Comparative effects of vasodilator drugs on flow distribution and venous return

Systemic vascular effects of hydralazine, prazosin, captopril, and nifedipine were studied in 115 anesthetized dogs. Blood flow (Q) and right atrial pressure (Pra) were independently controlled by a right heart bypass. Transient changes in central blood volume after an acute reduction in Pra at a constant Q showed that blood was draining from two vascular compartments with different time constants, one fast and the other slow. At three dose levels producing comparable reductions in systemic arterial pressure (30-40% at the highest dose), these drugs had different effects on flow distribution and venous return. Hydralazine and prazosin had parallel and balanced effects on arterial resistance of the two vascular compartments, and flow distribution was unaltered. Captopril preferentially reduced arterial resistance of the compartment with a slow time constant for venous return (-26 +/- 6%, -30 +/- 6%, -50 +/- 5% at 0.02, 0.10, and 0.50 mg X kg-1 X h-1, respectively; means +/- SEM) without altering arterial resistance of the fast time-constant compartment. Blood flow to the slow time-constant compartment was increased 43 +/- 14% at the highest dose, and central blood volume was reduced 108 +/- 15 mL. In contrast, nifedipine had a balanced effect on arterial resistance with the lowest dose (0.025 mg/kg) but caused a preferential reduction in arterial resistance of the fast time-constant compartment at higher doses (-38 +/- 4% and -55 +/- 2% at 0.05 and 0.10 mg/kg, respectively). Blood flow to the slow time-constant compartment was reduced 36 +/- 5% at the highest dose of nifedipine, and central blood volume was increased 66 +/- 12 mL. Total systemic venous compliance was unaltered or slightly reduced by each of the four drugs. These results add further evidence to the hypothesis that peripheral blood flow distribution is a major determinant of venous return to the heart.     

Role of renal nerves in development of hypertension in DOCA-salt model in rats: a telemetric approach

Centrally mediated hyperactivity of the autonomic nervous system contributes to DOCA hypertension; however, the targeted peripheral vascular bed(s) remain unclear. We propose that if renal sympathetic activity is a factor in the development of DOCA-salt hypertension, then renal denervation (RDNX) should attenuate the hypertensive response. In protocol 1, uninephrectomized RDNX (n = 9) and sham-denervated (n = 6) Sprague-Dawley rats were allowed free access to 0.9% NaCl solution and 0.1% NaCl diet. Mean arterial pressure (MAP) and heart rate were telemetrically recorded for 4 days before and 36 days after DOCA (100 mg/rat) implantation; sodium and water balances were recorded daily. Protocol 2 was similar except that saline intake in sham rats (n = 7) was matched to that observed in RDNX rats of protocol 1 for 30 days; for the last 10 days, the rats were allowed free access to saline. Before DOCA in protocol 1, MAP was lower (P < 0.05) in RDNX rats (99 +/- 1 mmHg) compared with sham rats (111 +/- 3 mmHg); however, heart rate and sodium and water balances were similar between groups. RDNX attenuated the MAP response to DOCA by approximately 50% (DeltaMAP = 22 +/- 3 mmHg, where Delta is change in MAP) when compared with sham rats (DeltaMAP = 38 +/- 6). RDNX rats consumed significantly less saline than sham rats, and cumulative sodium and water balances were reduced by 33% and 23%, respectively. In protocol 2, a similar pattern in MAP elevation was observed in RDNX and saline-restricted, sham-denervated rats even when saline restriction was removed. These results indicate that the renal sympathetic nerves are important in hypertension development but that other factors are also involved.     

Left ventricular reflex control of venous return and systemic vascular capacitance in dogs

The reflex effects of left ventricular distension on venous return, vascular capacitance, vascular resistance, and sympathetic efferent nerve activity were examined in dogs anesthetized with sodium pentobarbital. In addition, the interaction of left ventricular distension and the carotid sinus baroreflex was examined. Vascular capacitance was assessed by measuring changes in systemic blood volume, using extracorporeal circulation with constant cardiac output and constant central venous pressure. Left ventricular distension produced by balloon inflation caused a transient biphasic change in venous return; an initial small increase was followed by a late relatively large decrease. Left ventricular distension increased systemic blood volume by 3.8 +/- 0.6 mL/kg and decreased systemic blood pressure by 27 +/- 2 mmHg (1 mmHg = 133.3 Pa) at an isolated carotid sinus pressure of 50 mmHg. These changes were accompanied by a simultaneous decrease in sympathetic efferent nerve activity. When the carotid sinus pressure was increased to 125 and 200 mmHg, these responses were attenuated. It is suggested that left ventricular mechanoreceptors and carotid baroreceptors contribute importantly to the control of venous return and vascular capacitance.     

DOCA-salt hypertension in cats

The possibility of reproducing DOCA-salt hypertension in cats has been explored. It has been shown that administration of DOCA and sodium chloride may result in the development of a hypertensive condition in some of cats. Unilateral nephrectomy increases the probability of hypertension occurrence. To attain a steady and noticeable (up to 190 +/- 8/146 +/- 7 mm Hg) elevation of arterial pressure, it is necessary that appreciable amounts of DOCA and sodium chloride be administered for a long time (during 6 months) in the presence of unilateral nephrectomy. The hypertension thus induced is marked by the increased (71%) overall peripheral resistance and by the decreased cardiac output, which rises for a short period in the course of hypertension development.     

Influence of pregnancy on mean systemic filling pressure and the cardiac function curve in guinea pigs.

To assess the degree of circulatory fullness and to evaluate the influence of peripheral and cardiac factors in the regulation of cardiac output during pregnancy, the following studies were conducted using pentobarbital-anesthetized, open-chest nonpregnant and late term pregnant guinea pigs. Mean circulatory filling pressure was taken as the equilibrium pressure when the pulmonary artery was constricted. Total vascular compliance was assessed by +/- 5-mL changes in blood volume performed while this constriction was maintained. A separate group of guinea pigs was prepared with a pulmonary artery electromagnetic flow probe and right atrial catheter. Rapid infusion of saline was used to increase right atrial pressure while the cardiac output was determined. Pregnancy was characterized by the following changes relative to nonpregnant controls: 51Cr-labelled RBC blood volume increased from 55 +/- 3 to 67 +/- 3 mL/kg; mean circulatory filling pressure increased from 7.1 +/- 0.2 to 8.0 +/- 0.5 mmHg (1 mmHg = 133.322 Pa); right atrial pressure decreased from 3.4 +/- 0.2 to 2.1 +/- 0.3 mmHg; and cardiac output increased from 71.8 +/- 3.9 to 96.8 +/- 3.3 mL.min-1.kg-1. Total vascular compliance was not changed (2.1 +/- 0.1 mL.kg-1.mmHg-1) and most of the expanded blood volume was accommodated as unstressed volume. The cardiac function curve was shifted upwards in pregnant animals. The resistance to venous return, as determined from the slope of the venous return curves, was not changed. These data suggest that the circulation of the pregnant guinea pig is slightly overfilled.(ABSTRACT TRUNCATED AT 250 WORDS)     

Reflex control of vascular capacitance during hypoxia, hypercapnia, or hypoxic hypercapnia

We tested the hypothesis that the changes in venous tone induced by changes in arterial blood oxygen or carbon dioxide require intact cardiovascular reflexes. Mongrel dogs were anesthetized with sodium pentobarbital and paralyzed with veruronium bromide. Cardiac output and central blood volume were measured by indocyanine green dilution. Mean circulatory filling pressure, an index of venous tone at constant blood volume, was estimated from the central venous pressure during transient electrical fibrillation of the heart. With intact reflexes, hypoxia (arterial PaO2 = 38 mmHg), hypercapnia (PaCO2 = 72 mmHg), or hypoxic hypercapnia (PaO2 = 41; PaCO2 = 69 mmHg) (1 mmHg = 133.32 Pa) significantly increased the mean circulatory filling pressure and cardiac output. Hypoxia, but not normoxic hypercapnia, increased the mean systemic arterial pressure and maintained the control level of total peripheral resistance. With reflexes blocked with hexamethonium and atropine, systemic arterial pressure supported with a constant infusion of norepinephrine, and the mean circulatory filling pressure restored toward control with 5 mL/kg blood, each experimental gas mixture caused a decrease in total peripheral resistance and arterial pressure, while the mean circulatory filling pressure and cardiac output were unchanged or increased slightly. We conclude that hypoxia, hypercapnia, and hypoxic hypercapnia have little direct influence on vascular capacitance, but with reflexes intact, there is a significant reflex increase in mean circulatory filling pressure.     

Analysis of venous flow transients for estimation of vascular resistance, compliance, and blood flow distribution

We analysed venous flow transients using a long venous circuit and right heart bypass in 17 dogs after a rapid decrease in atrial pressure. A biphase curve was obtained which we decomposed into a two-compartment model, one with a fast time constant for venous return (0.069 min) and 52% of total circulating flow (Q), and one with a slower time constant (0.456 min) and 48% of Q. Subsequently, separate drainage from splanchnic and peripheral beds (with the renal venous return in the peripheral bed drainage) allowed comparison of time constants and venous outflow in these beds. The sum of the venous outflow volumes over time during separate drainage was indistinguishable from the single biphasic venous outflow volume curve over time observed with a long circuit and single reservoir. The fast time constant of the biphasic curve was not different from that determined by separate drainage from the peripheral circulation. The slow time constant of the single biphasic curve of 0.456 min was hybrid of two time constants, 0.216 min in the splanchnic bed and 0.862 min in the peripheral bed. Separate drainage from peripheral and splanchnic vascular beds demonstrated that the peripheral bed constituted 70% of venous outflow in the fast time constant compartment using Caldini's technique, whereas the splanchnic bed constituted 63% of venous outflow in the slow time constant compartment. It is concluded that, although Caldini's technique demonstrates biphasic venous flow transients, neither the fast nor the slow time constant compartments resolved from this analysis represent a particular anatomical region or vascular bed.     

Systemic arterial pressure response to two weeks of Tempol therapy in SHR: involvement of NO, the RAS, and oxidative stress

The roles of nitric oxide (NO) and plasma renin activity (PRA) in the depressor response to chronic administration of Tempol in spontaneously hypertensive rats (SHR) are not clear. The present study was done to determine the effect of 2 wk of Tempol treatment on blood pressure [mean arterial pressure (MAP)], oxidative stress, and PRA in the presence or absence of chronic NO synthase inhibition. SHR were divided into four groups: control, Tempol (1 mmol/l) alone, nitro-L-arginine methyl ester (L-NAME, 4.5 mg x g(-1).day(-1)) alone, and Tempol + L-NAME or 2 wk. With Tempol, MAP decreased by 22%: 191 +/- 3 and 162 +/- 21 mmHg for control and Tempol, respectively (P < 0.05). L-NAME increased MAP by 16% (222 +/- 2 mmHg, P < 0.01), and L-NAME + Tempol abolished the depressor response to Tempol (215 +/- 3 mmHg, P < 0.01). PRA was not affected by Tempol but was increased slightly with L-NAME alone and 4.4-fold with L-NAME + Tempol. Urinary nitrate/nitrite increased with Tempol and decreased with L-NAME and L-NAME + Tempol. Tempol significantly reduced oxidative stress in the presence and absence of L-NAME. In conclusion, in SHR, Tempol administration for 2 wk reduces oxidative stress in the presence or absence of NO, but in the absence of NO, Tempol is unable to reduce MAP. Therefore, NO, but not changes in PRA, plays a major role in the blood pressure-lowering effects of Tempol. These data suggest that, in hypertensive individuals with endothelial damage and chronic NO deficiency, antioxidants may be able to reduce oxidative stress but not blood pressure.     

Decreased NO signaling leads to enhanced vasoconstrictor responsiveness in skeletal muscle arterioles of the ZDF rat prior to overt diabetes and hypertension

Approximately 40% of patients with type 2 diabetes present with concurrent hypertension at the time of diabetes diagnosis. Increases in peripheral vascular resistance and correspondingly enhanced vasoconstrictor capacity could have profound implications for the development of hypertension and the progression of insulin resistance to overt diabetes. The purpose of this study was to determine whether skeletal muscle arteriolar vasoconstrictor dysfunction precedes or occurs concurrently with the onset of diabetes and hypertension. Male Zucker diabetic fatty (ZDF) rats were studied at 7, 13, and 20 wk of age to represent prediabetic and short-term and long-term diabetic states, respectively. Conscious mean arterial pressure (MAP), fasted plasma insulin and glucose, vasoconstrictor responses, and passive mechanical properties of isolated skeletal muscle arterioles were measured in prediabetic, diabetic, and age-matched control rats. Elevated MAP was manifest in short-term diabetes (control 117 +/- 1, diabetic 135 +/- 3 mmHg) and persisted with long-term diabetes (control 113 +/- 2, diabetic 135 +/- 3 mmHg). This higher MAP was preceded by augmented arteriolar vasoconstrictor responses to norepinephrine and endothelin-1 and followed by diminished beta-adrenergic vasodilation and enhanced myogenic constriction in long-term diabetes. Furthermore, we demonstrate that diminished nitric oxide (NO) signaling underlies the increases in vasoconstrictor responsiveness in arterioles from prediabetic and diabetic rats. Arteriolar stiffness was not different between control and prediabetic or diabetic rats at any time point studied. Collectively, these results indicate that increases in vasoconstrictor responsiveness resulting from diminished NO signaling in skeletal muscle arterioles precede the development of diabetes and hypertension in ZDF rats.     

Static filling pressure in patients during induced ventricular fibrillation

The static pressure resulting after the cessation of flow is thought to reflect the filling of the cardiovascular system. In the past, static filling pressures or mean circulatory filling pressures have only been reported in experimental animals and in human corpses, respectively. We investigated arterial and central venous pressures in supine, anesthetized humans with longer fibrillation/defibrillation sequences (FDSs) during cardioverter/defibrillator implantation. In 82 patients, the average number of FDSs was 4 +/- 2 (mean +/- SD), and their duration was 13 +/- 2 s. In a total of 323 FDSs, arterial blood pressure decreased with a time constant of 2.9 +/- 1.0 s from 77.5 +/- 34.4 to 24.2 +/- 5.3 mmHg. Central venous pressure increased with a time constant of 3.6 +/- 1.3 s from 7.5 +/- 5.2 to 11.0 +/- 5.4 mmHg (36 points, 141 FDS). The average arteriocentral venous blood pressure difference remained at 13.2 +/- 6.2 mmHg. Although it slowly decreased, the pressure difference persisted even with FDSs lasting 20 s. Lack of true equilibrium pressure could possibly be due to a waterfall mechanism. However, waterfalls were identified neither between the left ventricle and large arteries nor at the level of the diaphragm in supine patients. We therefore suggest that static filling pressures/mean circulatory pressures can only be directly assessed if the time after termination of cardiac pumping is adequate, i.e., >20 s. For humans, such times are beyond ethical options.     

Hemodynamic responses to static and dynamic muscle contractions at equivalent workloads

We tested the hypothesis that static contraction causes greater reflex cardiovascular responses than dynamic contraction at equivalent workloads [i.e., same tension-time index (TTI), holding either contraction time or peak tension constant] in chloralose-anesthetized cats. When time was held constant and tension was allowed to vary, dynamic contraction of the hindlimb muscles evoked greater increases (means +/- SE) in mean arterial pressure (MAP; 50 +/- 7 vs. 30 +/- 5 mmHg), popliteal blood velocity (15 +/- 3 vs. 5 +/- 1 cm/s), popliteal venous PCO(2) (15 +/- 3 vs. 3 +/- 1 mmHg), and a greater decrease in popliteal venous pH (0.07 +/- 0.01 vs. 0.03 +/- 0.01), suggesting greater metabolic stimulation during dynamic contraction. Similarly, when peak tension was held constant and time was allowed to vary, dynamic contraction evoked a greater increase in blood velocity (13 +/- 1 vs. -1 +/- 1 cm/s) without causing any differences in other variables. To investigate the reflex contribution of mechanoreceptors, we stretched the hindlimb dynamically and statically at the same TTI. A larger reflex increase in MAP during dynamic stretch (32 +/- 8 vs. 24 +/- 6 mmHg) was observed when time was held constant, indicating greater mechanoreceptor stimulation. However, when peak tension was held constant, there were no differences in the reflex cardiovascular response to static and dynamic stretch. In conclusion, at comparable TTI, when peak tension is variable, dynamic muscle contraction causes larger cardiovascular responses than static contraction because of greater chemical and mechanical stimulation. However, when peak tensions are equivalent, static and dynamic contraction or stretch produce similar cardiovascular responses.     

Pulmonary hemodynamics and lung water content during splanchnic ischemic shock

Pulmonary hemodynamics and lung water content were evaluated in open-chest dogs during splanchnic arterial occlusion (SAO) shock. Mean pulmonary arterial pressure [Ppa = 13.0 +/- 0.6 (SE) mmHg] and pulmonary venous pressure (4.1 +/- 0.2 mmHg) were measured by direct cannulation and the capillary pressure (Ppc = 9.0 +/- 0.6 mmHg) estimated by the double-occlusion technique. SAO shock did not produce a significant change in Ppa or Ppc despite a 90% decrease in cardiac output. An 18-fold increase in pulmonary vascular resistance occurred, and most of this increase (70%) was on the venous side of the circulation. No differences in lung water content between shocked and sham-operated dogs were observed. The effect of SAO shock was further evaluated in the isolated canine left lower lobe (LLL) perfused at constant flow and outflow pressure. The addition of venous blood from shock dogs to the LLL perfusion circuit caused a transient (10-15 min) increase in LLL arterial pressure (51%) that could be reversed rapidly with papaverine. In this preparation, shock blood produced either a predominantly arterioconstriction or a predominantly venoconstriction. These results indicate that both arterial and venous vasoactive agents are released during SAO shock. The consistently observed venoconstriction in the intact shocked lung suggests that other factors, in addition to circulating vasoactive agents, contribute to the pulmonary hemodynamic response of the open-chest shocked dog.     

Influence of positive airway pressure on the pressure gradient for venous return in humans.

To study the effect of positive airway pressure (Paw) on the pressure gradient for venous return [the difference between mean systemic filling pressure (Pms) and right atrial pressure (Pra)], we investigated 10 patients during general anesthesia for implantation of defibrillator devices. Paw was varied under apnea from 0 to 15 cmH(2)O, which increased Pra from 7.3 +/- 3.1 to 10.0 +/- 2.3 mmHg and decreased left ventricular stroke volume by 23 +/- 22%. Episodes of ventricular fibrillation, induced for defibrillator testing, were performed during 0- and 15-cmH(2)O Paw to measure Pms (value of Pra 7.5 s after onset of circulatory arrest). Positive Paw increased Pms from 10.2 +/- 3.5 to 12.7 +/- 3.2 mmHg, and thus the pressure gradient for venous return (Pms - Pra) remained unchanged. Echocardiography did not reveal signs of vascular collapse of the inferior and superior vena cava due to lung expansion. In conclusion, we demonstrated that positive Paw equally increases Pra and Pms in humans and alters venous return without changes in the pressure gradient (Pms - Pra).     

Regional venous outflow, blood volume, and sympathetic nerve activity during hypercapnia and hypoxic hypercapnia.

We examined the changes in systemic blood volume and regional venous outflow from the splanchnic, coronary, and other remaining vascular beds in response to acute hypercapnia or hypoxic hypercapnia in dogs, using cardiopulmonary bypass and a reservoir. Hypercapnia (PCO2 = 105 mmHg) (1 mmHg = 133 Pa) and hypoxic hypercapnia (PO2 = 23 mmHg, PCO2 = 99 mmHg) caused marked decreases in systemic blood volume of 14 +/- 3 and 16 +/- 3 mL/kg in spleen-intact dogs, and 3 +/- 2 and 10 +/- 2 mL/kg in splenectomized dogs, respectively. Splanchnic venous outflow increased by 12% at 3.5 min hypercapnia, whereas it decreased by 60% at 3.5 min hypoxic hypercapnia. Coronary venous outflow increased by 85 and 400% at 3.5 min hypercapnia and hypoxic hypercapnia, respectively. Sympathetic efferent nerve activity revealed a significant augmentation during hypoxic hypercapnia and a relatively smaller increase (30% of the response to hypoxic hypercapnia) during hypercapnia. Carotid and aortic chemoreceptor and baroreceptor denervation attenuated significantly the response of systemic blood volume to hypercapnia and hypoxic hypercapnia. The regional venous outflow responses to hypercapnia were not altered after chemodenervation, but those to hypoxic hypercapnia were significantly attenuated after chemodenervation. These results suggest that acute hypercapnia and hypoxic hypercapnia caused a marked decrease in vascular capacitance owing primarily to an increase in sympathetic efferent nerve activity via chemoreceptor stimulation. They also indicate that blood flow to the splanchnic vascular bed during hypercapnia increased (even though the cardiac output was constant), whereas it increased to the extrasplanchnic and coronary vascular beds during hypoxic hypercapnia.     

Effects of abdominal pressure on venous return: abdominal vascular zone conditions

The effects of changes in abdominal pressure (Pab) on inferior vena cava (IVC) venous return were analyzed using a model of the IVC circulation based on a concept of abdominal vascular zone conditions analogous to pulmonary vascular zone conditions. We hypothesized that an increase in Pab would increase IVC venous return when the IVC pressure at the level of the diaphragm (Pivc) exceeds the sum of Pab and the critical closing transmural pressure (Pc), i.e., zone 3 conditions, but reduce IVC venous return when Pivc is below the sum of Pab and Pc, i.e., zone 2 conditions. The validity of the model was tested in 12 canine experiments with an open-chest IVC bypass. An increase in Pab produced by phrenic stimulation increased the IVC venous return when Pivc-Pab was positive but decreased the IVC venous return when Pivc - Pab was negative. The value of Pivc - Pab that separated net increases from decreases in venous return was 1.00 +/- 0.72 (SE) mmHg (n = 6). An increase in Pivc did not influence the femoral venous pressure when Pivc was lower than the sum of Pab and a constant, 0.96 +/- 0.70 mmHg (n = 6), consistent with presence of a waterfall. These results agreed closely with the predictions of the model and its computer simulation. The abdominal venous compartment appears to function with changes in Pab either as a capacitor in zone 3 conditions or as a collapsible Starling resistor with little wall tone in zone 2 conditions.     

Hemodynamic effects of long-term converting-enzyme inhibition in renal hypertensive rats

The hemodynamic effects of a converting-enzyme inhibitor (CEI) given during 12 consecutive hours were studied in severe chronic renal hypertensive and normotensive Wistar rats. Hemodynamic parameters were obtained by thermodilution method in conscious unrestrained animals twenty-four hours after surgery. A bolus of CEI induced a significant decrease of mean arterial pressure (MAP) (from 192.2 +/- 8.2 to 163.3 +/- 5.9 mmHg, p less than 0.001) and total peripheral resistance (TPR) (from 7.69 +/- 0.53 to 5.83 +/- 0.33 mmHg.min/ml 100 g) in hypertensive animals. Cardiac index (CI) and heart rate increased significantly (p less than 0.05). Infusion of CEI to hypertensive animals during 12 consecutive hours produced a further progressive decrease in MAP and TPR (p less than 0.05) and an increase in CI (p less than 0.05). Heart rate did not change. Acute and prolonged infusions of CEI to normotensive group induced less but similar effect to those observed in hypertensive group. These results suggest that an increase of the renin-angiotensin system activity is the principal mechanism involved in the maintenance of high blood pressure during chronic phase of renal hypertension on the rats.     

Control of total peripheral resistance during hyperthermia in rats

To elucidate the effect of blood volume on the circulatory adjustment to heat stress, we studied alpha-chloralose-anesthetized rats at three levels of blood volume: normovolemia (NBV), hypervolemia (HBV; +32% plasma volume by isotonic albumin solution infusion), and hypovolemia (LBV; -16% plasma volume by furosemide administration). Body surface heating was performed with an infrared lamp to raise arterial blood temperature (Tb) at the rate of approximately 0.1 degree C/min. Before heating, central venous pressure (CVP) was significantly higher in HBV (0.41 +/- 0.25 mmHg) and lower in LBV (-1.44 +/- 0.22 mmHg) than in NBV (-0.41 +/- 0.10 mmHg). The Tb at which CVP started to decrease was approximately 40 degrees C in HBV, approximately 41 degrees C in NBV, and approximately 42 degrees C in LBV, and it decreased by 1.53 +/- 0.14, 1.92 +/- 0.24, and 0.62 +/- 0.14 mmHg from 37 to 43 degrees C of Tb in HBV, NBV, and LBV, respectively. Stroke volume was closely correlated with CVP, and this relationship was not affected by Tb. Heart rate responses to the raised Tb were similar among the three groups. Mean arterial pressure (MAP) was not affected by blood volume modification or CVP and was maintained at preheating (Tb 37 degrees C) level until Tb rose to 40 degrees C. Above this Tb, MAP increased until Tb reached 43 degrees C (+30-40 mmHg) for all three groups. Total peripheral resistance (TPR) was inversely correlated with CVP, and the slope of the linear relationship between TPR and CVP in LBV was three- to fourfold steeper than in NBV or HBV.(ABSTRACT TRUNCATED AT 250 WORDS)     

The haemodynamic and catecholamine response to xenon/remifentanil anaesthesia in Beagle dogs

The noble gas xenon seems to have minimal cardiovascular side-effects and so may be an ideal anaesthetic agent when investigating cardiovascular physiology. In comparison with standard modern anaesthetics, we investigated the haemodynamic and hormonal effects of xenon in Beagle dogs. After a 30 min baseline period, anaesthesia was induced with propofol and maintained with either (1) 1.2% isoflurane/70% nitrous oxide (N(2)O), (2) 0.8% isoflurane/0.5 microg/kg/min remifentanil or (3) 63% xenon/0.5 microg/kg/min remifentanil (n = 6 per group). Haemodynamics were recorded and blood samples taken before and 60 min after induction. Mean arterial blood pressure (MAP) was higher in conscious dogs than during isoflurane/N(2)O (86 +/- 2 vs. 65 +/- 2 mmHg, mean +/- SEM) and isoflurane/remifentanil anaesthesia (95 +/- 2 vs. 67 +/- 3 mmHg), whereas MAP did not decrease significantly in response to xenon/remifentanil anaesthesia (96 +/- 4 vs. 85 +/- 6 mmHg). Bradycardia was present during isoflurane/remifentanil (54 +/- 2/min) and xenon/remifentanil (40 +/- 3/min), but not during isoflurane/N(2)O anaesthesia (98 +/- 3/min, P < 0.05). Xenon/remifentanil anaesthesia induced the highest reduction in cardiac output (CO) (-61%), and the highest increase in systemic vascular resistance (+120%) among all treatment groups (P < 0.05). A simultaneous increase in endogenous adrenaline and noradrenaline concentrations could only be observed in the xenon/remifentanil group, whereas angiotensin II and vasopressin concentrations increased in all groups. In conclusion, xenon/remifentanil anaesthesia maintains MAP but reduces heart rate and CO and is associated with a considerable stimulation of vasopressor hormones in Beagle dogs. Therefore, xenon/remifentanil exerts a new quality of adverse haemodynamic effects different from volatile anaesthetics and may not perform better during studies of cardiovascular physiology.     

Heme oxygenase-mediated endothelial dysfunction in DOCA-salt, but not in spontaneously hypertensive, rat arterioles

Vascular heme oxygenase (HO) metabolizes heme to form carbon monoxide. Carbon monoxide inhibits nitric oxide synthase and promotes endothelium-dependent vasoconstriction. We reported HO-1-mediated endothelial dysfunction in Dahl salt-sensitive hypertension. Previous studies suggested that salt-sensitive hypertensive rats, but not spontaneously hypertensive rats (SHR), display endothelial dysfunction. This study examines the hypothesis that HO-1-mediated arteriolar endothelial dysfunction develops in deoxycorticosterone acetate (DOCA)-salt hypertensive (DOCA) rats, but not in SHR. Uninephrectomized (isoflurane anesthesia) male Sprague-Dawley rats received DOCA injections and saline drinking solution for 4 wk. Rats subjected to sham surgery received vehicle injections and tap water. Blood pressure was elevated in DOCA rats and SHR compared with sham and Wistar-Kyoto (WKY) groups. Aortic HO-1 expression and blood carboxyhemoglobin levels were elevated in the DOCA group, but not in SHR. In isolated gracilis muscle arterioles, ACh caused concentration-related vasodilation in all groups, with attenuated maximum responses in DOCA, but not in SHR, arterioles. Acute pretreatment with an inhibitor of HO, chromium mesoporphyrin, restored ACh-induced responses in DOCA arterioles to sham levels. ACh responses remained the same in SHR and WKY arterioles after chromium mesoporphyrin treatment. These data show that HO-1 levels and activity are increased and arteriolar responses to ACh are decreased in DOCA rats, but not in SHR. Furthermore, in DOCA arterioles, an inhibitor of HO restores ACh-induced vasodilation to sham levels. These results suggest that elevated HO-1 levels and activity, not resulting from hypertension per se, contribute to endothelial dysfunction in DOCA rats.     

Effects of chronic baroreceptor unloading on blood pressure in the dog

We have developed a new model of chronic baroreceptor unloading (CBU) in the dog. Initial characterization of the model indicated that CBU increased mean arterial pressure (MAP) by an average of 22 mmHg for 7 days. The goal of the present study was to replicate the previous study using telemetry to record MAP continuously and to determine the effects of CBU (n = 7) on chronic regulation of MAP. We also prepared a group of dogs with sinoaortic denervation (SAD, n = 6) to compare the time course of changes in MAP in the two models. Control levels (7 day average +/- SE) of MAP in the CBU and SAD groups were 94 +/- 2 and 94 +/- 1 mmHg, respectively. MAP averaged 124 +/- 8 and 103 +/- 4 mmHg during the first and second weeks after SAD (both P < 0.05) and then declined to levels not different from control during weeks 3-5. In the CBU group, MAP averaged 120 +/- 4 mmHg during the first week, declined to 111 +/- 4 mmHg during the second week, and stabilized at 104 mmHg during weeks 3-5 (all P < 0.05 compared with control). Plasma norepinephrine levels were increased significantly for the first week after SAD and for 2 wk after CBU but were not different from control for the remainder of the study. These results indicate that the initial increase in MAP after CBU is not sustained but declines to a level that is modestly higher than control. However, because MAP did not fall to control levels, the results are compatible with the hypothesis that baroreceptor input can influence the long-term level of MAP.