Plasmodium berghei: malaria infection causes increased cardiac output in rats, Rattus rattus

Thirty-two 4-week-old male Wistar rats were infected with Plasmodium berghei malaria. On Days 12 through 14, blood volume, arterial blood pressure, right ventricular pressure, heart rate, cardiac output, stroke volume, hematocrit, and vascular resistances were determined. All of the cardiovascular parameters measured, with the exception of calculated pulmonary vascular resistance, changed progressively as the peripheral blood parasitemia increased. With a rising parasitemia, cardiac output increased, despite a reduced heart rate. The highest parasitemia of 63% was accompanied by a doubling of the normal cardiac output. The relationship between parasitemia and cardiac output can be described by the equation, cardiac output = (6.14) x % parasitemia + 452 ml/min/kg. The mean arterial blood pressure was lower than controls when parasitemia exceeded 20%, whereas systolic right ventricular pressure was elevated only at the highest parasitemias. When noninfected control rats were compared with those animals having parasitemias greater than 40%, in the infected animals, mean arterial pressure was 28% lower (P less than 0.01) and systolic right ventricular pressure rose by 21% (P less than 0.02). A 50% decline was observed in the total peripheral vascular resistance (P less than 0.01), although the pulmonary resistance was apparently unchanged. With P. berghei infection, there is also a marked anemia, an increase in plasma volume, and a 16% increase in blood volume (% body weight). It is concluded from these results that although the hemodynamic changes previously reported in the literature indicate that infection with malaria may result in focal blockages in microvessels and poor tissue perfusion, the total systemic effect, in the rat, is an increase in cardiac output secondary to a reduced peripheral resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced maximal metabolic vasodilatation in the dominant forearms of tennis players

In an effort to evaluate potential peripheral adaptations to training, maximal metabolic vasodilation was studied in the dominant and nondominant forearms of six tennis players and six control subjects. Maximal metabolic vasodilation was defined as the peak forearm blood flow measured after release of arterial occlusion, the reactive hyperemic blood flow (RHBF). Two ischemic stimuli were employed in each subject: 5 min of arterial occlusion (RHBF5) and 5 min of arterial occlusion coupled with 1 min of ischemic exercise (RHBF5ex). RHBF and resting forearm blood flows were measured using venous occlusion strain-gauge plethysmography (ml X min-1 X 100 ml-1). Resting forearm blood flows were similar in both arms of both groups. RHBF5ex was similar in both arms of our control group (dominant, 40.8 +/- 1.2 vs. nondominant, 40.9 +/- 2.1). However, RHBF5ex was 42% higher in the dominant than in the nondominant forearms of our tennis player population (dominant, 48.7 +/- 4.0 vs. nondominant, 34.4 +/- 3.4; P less than 0.05). This intraindividual difference in peak forearm blood flows was not secondary to improved systemic conditioning since the maximal O2 consumptions in the two study groups were similar (controls, 45.4 +/- 3.9 vs. tennis players, 46.1 +/- 1.7). These findings suggest a primary peripheral cardiovascular adaptation to exercise training in the dominant forearms of the tennis players resulting in a greater maximal vasodilatation.     

Relations between the renin-angiotensin-aldosterone system and urinary elimination of sodium: study of healthy subjects in clinostatism and on a sodium-free diet

In 94 normotensive subjects and free sodium diet, the relationship between SPRA and the 2-hour urinary sodium excretion was significantly better fitted by an hyperbolic function (p less than 0,001); r = 0,53) than a linear one (p less than 0,001; r = -0,31) between SPRA and the 24-hour urinary sodium excretion. (SPRA = Supine Plasma Renin Activity).     

Long-lasting vasoconstriction and efficient regional extraction of endothelin-1 in human splanchnic and renal tissues

Six healthy subjects were given endothelin-1, intravenously in a dose of 4 pmol.kg-1.min-1 for 20 min. Blood samples were drawn from arterial, hepatic and renal vein catheters for determinations of splanchnic and renal blood flows and the extraction of endothelin-1 in these vascular beds. Intravenous infusion of endothelin-1 increased the mean arterial blood pressure by 6.8 +/- 2.0 mm Hg (p less than 0.05) and reduced splanchnic and renal blood flows by 34% (p less than 0.005) and 26% (p less than 0.001) respectively. Return to basal flow values occurred after about 1 hr for the splanchnic and 3 hrs for the renal blood flow. The fractional extractions of endothelin-1-like immunoreactivity corresponded to 75 +/- 2% and 60 +/- 2% in the splanchnic and renal vascular beds, respectively. The disappearance curve in plasma and two half-lives of 1.4 +/- 0.1 min and 35 +/- 2.8 min respectively.     

Effects of adenosinergic drugs on hypoxia-induced electrophysiological changes in rat hippocampal slices.

The effects of adenosinergic antagonists caffeine and DPCPX, and of the adenosinergic agonists L-PIA, CPA and CGS 21680 were investigated on fully and partially reversible hypoxia-induced electrophysiological changes in rat hippocampal slices. The influence of a high potassium solution and of the N-methyl-D-aspartate antagonist dizocilpine (MK 801) was also tested. The latency to obtain a 50% decrease in the amplitude of the CA1 population spike (CA1 PS) during a short- (5-10 min) lasting hypoxic period was significantly increased (P less than 0.01) by slice perfusion with caffeine (50 microM), DPCPX (0.2 microM), and by increasing (from 3 to 4 mM) the potassium concentration in the medium bathing the hippocampal slices. The latency was significantly decreased (P less than 0.01) by slice perfusion with L-PIA (0.2 microM) and CPA (0.05 microM). It was not significantly modified by CGS 21680 (5 microM). The incidence of reappearance of the CA1 PS during reoxygenation after long- (45 min) lasting hypoxia was significantly increased (P less than 0.05) by slice perfusion with MK 801 (50 microM), while it was not significantly affected by slice perfusion with caffeine (50 microM) or DPCPX (0.2 microM) or L-PIA (0.2 microM) or CPA (0.05 microM) or CGS 21680 (5 microM). The results indicate a prevalent involvement of the A1 adenosine receptors in the early mechanisms underlying hypoxia-induced reversible changes. Adenosine seems to have a limited role in the late mechanisms occurring after a long-lasting hypoxic period.     

Lipid peroxides and atherosclerosis.

Plasma lipid peroxide concentrations were measured in 100 patients with occlusive arterial disease proved angiographically (50 patients with ischaemic heart disease, 50 with peripheral arterial disease) and compared with values in 75 control patients with no clinical evidence of atherosclerosis. Lipid peroxide concentrations were significantly higher in patients both with ischaemic heart disease (median 4.37 mumol/l (interquartile range 3.85-5.75 mumol/l); p less than 0.001) and with peripheral arterial disease (median 4.37 mumol/l (3.88-5.21 mumol/l); p less than 0.001) than in controls (median 3.65 mumol/l (interquartile range 3.29-3.89 mumol/l). Overall there was a significant but weak correlation between plasma lipid peroxide and plasma triglyceride concentrations (rs = 0.25; p less than 0.001) but not between plasma lipid peroxide and plasma total cholesterol concentrations. Furthermore, hypertension, obesity, diabetes, smoking, positive family history, and intake of beta blockers and thiazide diuretics were not associated with significant differences in lipid peroxide values. This study provides clinical support to experimental data indicating that peroxidised lipids may be important in atherogenesis and its complications and also suggests that peroxidised lipids may provide an index of the severity of atherosclerosis.     

Distribution of blood flow during exercise after blood volume expansion in swine

To study the distribution of blood flow after blood volume expansion, seven miniature swine ran at high speed (17.6-20 km/h, estimated to require 115% of maximal O2 uptake) on a motor-driven treadmill on two occasions: once during normovolemia and once after an acute 15% blood volume expansion (homologous whole blood). O2 uptake, cardiac output, heart rate, mean arterial pressure, and distribution of blood flow (with radiolabeled microspheres) were measured at the same time during each of the exercise bouts. Maximal heart rate was identical between conditions (mean 266); mean arterial pressure was elevated during the hypovolemic exercise (149 +/- 5 vs. 137 +/- 6 mmHg). Although cardiac output was higher and arterial O2 saturation was maintained during the hypervolemic condition (10.5 +/- 0.7 vs. 9.3 +/- 0.6 l/min), O2 uptake was not different (1.74 +/- 0.08 vs. 1.74 +/- 0.09 l/min). Mean blood flows to cardiac (+12.9%), locomotory (+9.8%), and respiratory (+7.5%) muscles were all elevated during hypervolemic exercise, while visceral and brain blood flows were unchanged. Calculated resistances to flow in skeletal and cardiac muscle were not different between conditions. Under the experimental conditions of this study, O2 uptake in the miniature swine was limited at the level of the muscles during hypervolemic exercise. The results also indicate that neither intrinsic contractile properties of the heart nor coronary blood flow limits myocardial performance during normovolemic exercise, because both the pumping capacity of the heart and the coronary blood flow were elevated in the hypervolemic condition.     

The hypothetical role of potassium conductance on the genesis of R-wave amplitude increase during ischemia in the isolated rat heart.

The effect of increased potassium conductance on the genesis of R-wave amplitude increase during acute myocardial ischemia has been studied in the isolated perfused rat heart by simultaneously recording the R-wave amplitude of epicardial electrograms (VEE), heart rate (HR), coronary flow rate (CFR), left ventricular diastolic pressure (LVDP), and left ventricular systolic pressure (LVSP). The experiments were performed during basal and partial or total ischemic conditions at spontaneous or fixed HR. In some experiments, potassium conductance was increased by means of high-calcium (8 mM) or acetylcholine chloride (10(-6) M) perfusion. In the control experiments, partial ischemic perfusion produced an increase in VEE and LVDP and a decrease in HR, CFR, and LVSP; total ischemic perfusion exaggerated these variations. High-calcium perfusion provoked an increase in VEE and LVDP and a decrease in HR, CFR, and LVSP during basal conditions (p less than 0.01 vs. control experiment); these modifications increased progressively during partial ischemic perfusion (p less than 0.01 vs. control experiment) and during total ischemic perfusion (p less than 0.01 vs. control experiment). Perfusion with acetylcholine chloride produced variations similar to those observed in high-calcium solution except that LVDP under basal conditions remained unchanged from control. When the HR was maintained at a constant value by means of atrial pacing the results were similar to those observed in the unpaced hearts. In conclusion, in the isolated perfused rat heart, increasing potassium conductance may influence the genesis of R-wave amplitude increasing during acute myocardial ischemia.     

Pattern differences between distributions of microregional myocardial flows in crystalloid- and blood-perfused rat hearts

Regional myocardial flow distributions in Langendorff rat hearts under Tyrode and blood perfusion were assessed by tracer digital radiography (100-microm resolution). Flow distributions during baseline and maximal hyperemia following a 60-s flow cessation were evaluated by the coefficient of variation of regional flows (CV; related to global flow heterogeneity) and the correlation between adjacent regional flows (CA; inversely related to local flow randomness). These values were obtained for the original images (64(2) pixels) and for coarse-grained images (32(2), 16(2), and 8(2) blocks of nearby pixels). At a given point in time during baseline, both CV and CA were higher in blood (n = 7) than in Tyrode perfusion (n = 7) over all pixel aggregates (P < 0.05, two-way ANOVA). During the maximal hyperemia, CV and CA were still significantly higher in blood (n = 7) than in Tyrode perfusion (n = 7); however, these values decreased substantially in blood perfusion and the CV and CA differences became smaller than those at baseline accordingly. During basal blood perfusion, the 60-s average flow distribution (n = 7) showed a smaller CV and CA than those at a given point in time (P < 0.05, two-way ANOVA). Coronary flow reserve was significantly higher in blood than in Tyrode perfusion. In conclusion, the flow heterogeneity and the local flow similarity are both higher in blood than in Tyrode perfusion, probably due to the different degree of coronary tone preservation and the presence or absence of blood corpuscles. Under blood perfusion, temporal flow fluctuations over 60-s order are largely involved in shaping microregional flow distributions.     

Response of thyrotropin, prolactin and free thyroid hormones to graded exercise in normal male subjects

Serum levels of thyrotrophin (TSH), prolactin (PRL), free thyroxine (FT4) and free triiodothyronine (FT3) were determined before and after physical exercise in 21 normal male subjects. The subjects were divided into 3 groups as follows: group I--light exercise (exercise on the Mijnhardt bicycle ergometer at 100 Watts for 15 min); group II--moderate exercise (a 5 km marathon); group III--heavy exercise (a 10 km marathon). In group I, TSH level rose from 1.96 +/- 0.42 mu u/ml (mean +/- SEM) to 2.52 +/- 0.30 mu u/ml (p less than 0.01), and PRL levels rose from 11.0 +/- 2.0 ng/ml to 19.0 +/- 5.2 ng/ml (p less than 0.01). In group II, TSH rose from 2.11 +/- 0.51 mu u/ml to 2.62 +/- 0.56 mu u/ml (p less than 0.05), and PRL rose from 11.2 +/- 1.6 ng/ml to 24.0 +/- 5.2 ng/ml (p less than 0.01). In group III, TSH rose from 2.01 +/- 0.41 mu u/ml to 2.36 +/- 0.45 mu u/ml (p less than 0.02), and PRL rose from 12.1 +/- 2.0 ng/ml to 47.7 +/- 9.3 ng/ml (p less than 0.01). The serum levels of FT4 showed different results among the three groups: Group I showed an increased response from 1.60 +/- 0.12 ng/dl to 1.72 +/- 0.12 ng/dl (p less than 0.01); Group II showed no significant difference; and group III demonstrated a diminished response from 1.61 +/- 0.14 ng/dl to 1.45 +/- 0.16 ng/dl (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of elimination of brain stem-septal connections on prolonged posttetanic changes in the hippocampus

Comparative analysis of long-lasting effects of Schaffer's collaterals tetanization (15 Hz, 15 s) was performed in 61 extracellularly recorded units of the intact hippocampus (field CA1) and in 51 units after complete septo-hippocampal disconnection in chronic alert rabbits. The number of units with long-lasting potentiation (LLP) was significantly greater in the hippocampus deprived of brain stem-septal afferents (63%) as compared to the intact hippocampus (21%); the number of units with posttetanic depression was reduced (21% versus 34%). The mean level of LLP in the deafferentated hippocampus was significantly higher than in the intact hippocampus (mean 220% and 180% of control level; p less than 0,001), and its duration was greater. Conversely, the mean level of depression was lower in the deafferentated hippocampus than in the normal one (140% and 170% of control level; p less than 0,01). This increase of LLP may result from elimination of inhibitory influences of the brain stem-septal afferent input, and/or from sprouting of Schaffer's collaterals after deafferentation with increase in number of functional synapses.     

Reductions in blood pressure after acute exercise by hypertensive rats

Postexercise reductions in blood pressure at rest have been reported for hypertensive subjects. To determine whether post-exercise hypotension would occur in spontaneously hypertensive rats and to test the hypothesis that any reductions would result because of decreases in regional vascular resistances, hypertensive rats (n = 19) were instrumented with indwelling arterial catheters and Doppler probes to measure regional blood flows from the iliac, superior mesenteric, and renal arteries. Data were collected from animals who performed a 20- and a 40-min treadmill test at between 60 and 70% of their maximum O2 uptake. When the animals ran for 20 min, there was a pre- to postexercise drop in mean arterial pressure (MAP) from 158 +/- 3.6 to 150 +/- 3.6 mmHg (P less than 0.05), which was recorded 30 min after the exercise had ceased. The pre- to postexercise reduction in MAP after 40 min of treadmill running was from 154 +/- 3.1 to 138 +/- 3.0 mmHg (P less than 0.05) as recorded 30 min postexercise. Postexercise heart rate was significantly lower after the 40-min exercise bout, from a preexercise mean of 351 +/- 3 beats/min to 324 +/- 5 beats/min 30 min after the treadmill had stopped. Surprisingly, marked pre- to postexercise reductions in regional vascular resistance were not observed in either the iliac, superior mesenteric, or renal vascular beds. These data demonstrated the existence of postexercise hypotension in genetic hypertensive rats and suggested that reductions in cardiac output were the primary hemodynamic mechanism for this finding.     

Vascular flow capacity of hindlimb skeletal muscles in spontaneously hypertensive rats

Total and regional skeletal muscle flows (radiolabeled microspheres) were determined in isolated maximally vasodilated hindquarters of spontaneously hypertensive rats (SHR) and age-matched (11-12 mo) normotensive Wistar-Kyoto rats (WKY) to assess the vascular flow capacity of the skeletal muscle vascular beds. Vascular flow capacity was estimated by measuring total hindquarters and regional muscle blood flows (under conditions of maximal vasodilation with papaverine or papaverine plus isoproterenol) over a wide range of perfusion pressures in WKY and SHR. Capillary exchange capacity was estimated by determining the capillary filtration coefficient. Isogravimetric capillary pressures and segmental vascular resistances were determined in each hindquarter. Isogravimetric flows and capillary pressures were not different between WKY and SHR. However, total and precapillary vascular resistances were significantly elevated in SHR, and postcapillary resistances were not different compared with WKY. Maximal capillary filtration coefficient values for the SHR group averaged 20% lower than WKY values, suggesting that hypertension was associated with a reduction in the microvascular surface area available for fluid exchange and, therefore, the capillary exchange capacity. Over the perfusion pressures studied, total hindquarters flows averaged 60% lower in SHR than in WKY. Flows to individual skeletal muscles averaged 76% lower in SHR than in WKY regardless of the muscle fiber type. Thus, modifications exist in the hindlimb skeletal muscle vasculature of SHR that reduces the capillary exchange capacity and limit the capacity of deliver flow at a given perfusion pressure gradient.     

The role of leukotrienes in the late hemodynamic manifestations of group B streptococcal sepsis in piglets

In order to evaluate the role of leukotrienes in group B streptococcal (GBS) sepsis we studied the effect of a leukotriene receptor antagonist, FPL 57231, on the late hemodynamic changes occurring secondary to an infusion of live GBS. Paralyzed, mechanically ventilated piglets received a continuous intravenous infusion of bacteria (5 x 10(7) org/kg/min) while systemic arterial (Psa) and pulmonary artery pressures (Ppa) were measured. To separate the effects of the lipoxygenase products of arachidonic acid from those of the cyclooxygenase by-products, animals in control and treatment groups received indomethacin, a cyclooxygenase blocking agent, 15 min after the infusion of GBS was begun. In addition to GBS and indomethacin, treatment animals received a 30 min infusion of FPL 57231 starting 120 min after the bacterial infusion was begun. All study animals responded to bacteria within 15 min with marked elevation in pulmonary artery pressure (X +/- SD) (12 +/- 3 to 49 +/- 5 mmHg; p less than .01), and a decline in PaO2 (84 +/- 9 to 49 +/- 5 mmHg; p less than .01) and cardiac output (0.29 +/- 0.04 to 0.18 +/- .07 liter/min/kg; p less than .01). These changes were reversed by indomethacin. Subsequent values remained relatively stable until approximately 90 min when a gradual decrease in cardiac output (CO) and PaO2, and an increase in Ppa, and calculated systemic (SVR) and pulmonary (PVR) vascular resistances occurred. After the initial increase in TxB2 and 6-keto-PGF1 alpha, indomethacin treatment resulted in return of these values to baseline with no further increase throughout the study period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Myocardial flow distribution. II : Empty beating heart, ventricular fibrillation and cardiac arrest

Myocardial oxygen consumption (MVO2) and coronary blood flow (CBF) distribution were studied in 21 isolated, metabolically supported dog hearts. Measurements of MVO2 and CBF distribution were carried out in three different experimental conditions : empty beating heart (EBH), ventricular fibrillation (VF) and high potassium-induced cardiac arrest (CA). MVO2 was approximately the same in EBH and VF (4.09 +/- 0.77 and 4.28 +/- 0.68 ml O2 min-1 100 g-1 respectively), and significantly lower in the group with CA (2.40 +/- 0.18 ml O2 min-1 100 g-1, P less than 0.05). Total CBF showed no significant differences among the three groups (84 +/- 7 ml/min in EBH; 78 +/- 7 ml/min in VF and 83 +/- 7 ml/min in CA). Subendocardial CBF per unit of tissue mass was significantly lower in hearts with VF (0.43 +/- 0.01 ml/min-1 g-1, P less than 0.05) when tested against the other two groups of experiments (0.69 +/- 0.03 ml min-1 g-1 in EBH and 0.65 +/- +/- 0.04 ml min-1 g-1 in CA). This was also reflected in the endo/epi ratio, that was significantly lower in VF (1.41 +/- 0.07, P less than 0.05) with respect to the other two groups (2 +/- 0.09 in EBH and 2.21 +/- 0.07 in CA). From data presented here we can conclude that cardioplegia, even in absence of hypothermia, is a method that will assure myocardial protection providing : (1) a lower subendocardial MVO2; (2) a higher subendocardial CBF, which helps for a prompt recovery during reperfusion.     

Ascorbate improves circulation in postural tachycardia syndrome

Low flow postural tachycardia syndrome (LFP) is associated with vasoconstriction, reduced cardiac output, increased plasma angiotensin II, reduced bioavailable nitric oxide (NO), and oxidative stress. We tested whether ascorbate would improve cutaneous NO and reduce vasoconstriction when delivered systemically. We used local cutaneous heating to 42°C and laser Doppler flowmetry to assess NO-dependent conductance (%CVC(max)) to sodium ascorbate and the systemic hemodynamic response to ascorbic acid in 11 LFP patients and in 8 control subjects (aged 23 ± 2 yr). We perfused intradermal microdialysis catheters with sodium ascorbate (10 mM) or Ringer solution. Predrug heat response was reduced in LFP, particularly the NO-dependent plateau phase (56 ± 6 vs. 88 ± 7%CVC(max)). Ascorbate increased baseline skin flow in LFP and control subjects and increased the LFP plateau response (82 ± 6 vs. 92 ± 6 control). Systemic infusion experiments used Finometer and ModelFlow to estimate relative cardiac index (CI) and forearm and calf venous occlusion plethysmography to estimate blood flows, peripheral arterial and venous resistances, and capacitance before and after infusing ascorbic acid. CI increased 40% after ascorbate as did peripheral flows. Peripheral resistances were increased (nearly double control) and decreased by nearly 50% after ascorbate. Calf capacitance and venous resistance were decreased compared with control but normalized with ascorbate. These data provide experimental support for the concept that oxidative stress and reduced NO possibly contribute to vasoconstriction and venoconstriction of LFP.     

A fast-acting humoral factor mediates pressor hyperresponsiveness in deoxycorticosterone-salt rabbits

Six rabbits were sham operated and were given water to drink (sham-water group); six additional rabbits were sham operated and were given saline to drink (sham-salt group); another six rabbits received an implant of deoxycorticosterone (DOCA) and were given water to drink (DOCA-water group); a final group of six rabbits received implants of DOCA and were given saline to drink (DOCA-salt group). Two weeks later, all four groups of rabbits had approximately the same mean arterial pressures, and the sham-salt, DOCA-water, and DOCA-salt groups all had plasma renin activity values less than the sham-water group. The DOCA-salt group had greater pressor responses to norepinephrine (NE) at several doses than did the other three groups of rabbits. In another group of six sham-water and six DOCA-salt rabbits, measurements of cardiac output before and during infusions of NE at 800 ng/min/kg body wt revealed no changes in cardiac output before or during NE infusion, but the DOCA-salt group had significantly greater increases in mean arterial pressure and total peripheral resistance during NE than did the sham-water group. In another group of six DOCA-salt rabbits, the pressor response to several doses of NE were determined during infusion of the angiotensin II (AII) antagonist, [Sar1, Ile8] AII; this AII antagonist failed to alter the enhanced pressor responses to NE. A final experiment examined pressor responses to NE in six normal rabbits before and after cross circulation of blood with six DOCA-salt rabbits. After blood cross circulation the normal rabbits had exaggerated pressor responses to NE at 5, 15, and 30 min, but not at 60 min. Similar cross-circulation experiments between six pairs of normal rabbits did not show any transfer of pressor hyperresponsiveness. These studies indicated that pressor and vascular hyperresponsiveness in DOCA-salt rabbits is conveyed by a fast-acting hormonal factor and that AII probably is not involved in mediating this hyperresponsiveness.     

Placental vascular responses to leukotriene receptor antagonist FPL 55712

We have previously shown that FPL 55712, a specific leukotriene receptor antagonist, potentiates estrogen induced uterine hyperemia in nonpregnant rabbits. We therefore chose to investigate the vascular responses of pregnant rabbits to leukotriene blockade. Nine unanesthetized animals carrying 46 viable fetuses were used in this study. Regional blood flows were measured by the radioactive microsphere technique. In 5 rabbits control blood flows were measured after vehicle administration and FPL 55712, 1 mg/kg bolus, followed by infusion of 100 micrograms/kg/min was given via the jugular vein. Regional blood flows were measured again after 10 minutes of infusion. The procedural order was reversed in the remaining 4 animals. Resistance was calculated as mean arterial pressure divided by total flow to an organ. FPL 55712 decreased the blood pressure from 83 +/- 2 to 76 +/- 3 mmHg (P less than .001). Uterine resistance was not significantly changed (387 +/- 44 to 362 +/- 42 mmHg X ml-1 X min X gm), but renal resistance fell from 18.5 +/- 1.1 to 15.1 +/- 1.2 mmHg X ml-1 X min X gm (P less than .01). FPL 55712 induced maternal placental vasodilatation with resistance decreasing from 291 +/- 33 to 261 +/- 31 mmHg X ml-1 X min X gm (P less than .04). Vehicle administration did not cause dilation in any vascular bed. FPL 55712 appears to be a placental vasodilator whose action is most likely due to receptor blockade of the vasoconstrictive endogenous leukotrienes.     

Systemic methionine-enkephalin evokes cardiostimulatory responses in the human

The cardiovascular effects of bolus doses of methionine-enkephalin (Met5-ENK) (1 to 100 micrograms/kg) were studied in 9 subjects in whom, at cardiac catheterization for evaluation of chest pain, patent coronary arteries were found. Met5-ENK produced a simultaneous increase in blood pressure and heart rate beginning within 20 sec, reaching maximal values between 30 and 40 sec, and then terminating by 60 sec. Heart rate, systolic, diastolic, and mean arterial blood pressures increased significantly (p less than 0.0005); pulse pressure remained unchanged. Positive dose-effect relationships were observed for heart rate (p less than 0.002), systolic, diastolic, and mean arterial blood pressures (p less than 0.05). Naloxone (0.5 mg/kg), given to 4 subjects, prevented the heart rate and blood pressure changes associated with Met5-ENK administration, demonstrating that the cardiovascular changes were mediated by opiate receptors. Subjects also described cutaneous paresthesias which were not prevented by naloxone pretreatment. These data suggest a role for peripheral enkephalins in cardiovascular regulation.     

ETA endothelin receptors are involved in the ouabain-induced haemodynamic effects in the periaqueductal gray area of rats

The aim of the present study was to asses the effects on blood pressure and vascular resistances elicited by microinjections of ouabain (OUA) within the periaqueductal gray area (PAG). We also tested whether peripheral vascular responses caused by exogenous intra-PAG ouabain involve activation of the PAG-endothelin system.In normotensive Sprague-Dawley rats the basal mean arterial blood pressure (MABP) was 114 +/- 3 mmHg. This was significantly increased by OUA (3 micro g, 122 +/- 2 mmHg, p < 0.05; and 6 micro g, 139 +/- 3 mmHg, p < 0.01) microinjected into the PAG area. Increases in MABP were associated with increases in total peripheral resistances (TPR), organ vascular resistances, and with reduced blood flow of almost all the organs tested: kidneys, skeletal muscle, skin, stomach, spleen, testes and intestine. Cardiac output did not change.Changes in the above vascular parameters induced by OUA were significantly (p < 0.01) reduced by intra-PAG microinjections of FR139317 (a selective ETA receptor antagonist, 5 nmol), SB209670 (a non-selective ETA/ETB receptor antagonist, 3 nmol), but not by BQ 788 (a selective ETB receptor antagonist, 5 nmol).In conclusion, OUA into the PAG area of normotensive rats caused significant changes in peripheral vascular parameters that are reduced by ETA receptor antagonists. These results indicate that PAG-ET-1 system via an action on ETA receptors is involved in the OUA effects.