Cardiac and regional haemodynamic effects of endothelin-1 in rats subjected to critical haemorrhagic hypotension.

In the present study, we examined cardiac and regional haemodynamic effects of endothelin-1 (ET-1), a potent vasoconstrictive factor, in a rat model of pressure-controlled irreversible haemorrhagic shock resulting in the death of all control animals within 30 min. Experiments were carried out in male ethylurethane-anaesthetised Wistar rats subjected to hypotension of 20-25 mmHg, which resulted in bradycardia, an extreme decrease in cardiac index (CI) and an increase in total peripheral resistance index (TPRI), with reductions in renal (RBF), hindquarters (HBF) and mesenteric blood flow (MBF). ET-1 (50, 200 pmol/kg) administered intravenously at 5 min of critical hypotension produced increases in mean arterial pressure (MAP) and heart rate (HR), which were significantly higher than those in normotensive animals, and a 100% survival at 2 h after treatment. The effects were accompanied by a rise in CI, a decrease in TPRI, with increases in RBF and HBF and persistently lowered MBF, and an increase in circulating blood volume 20 min after treatment. The cardiovascular effects of ET-1 were inhibited by the ETA receptor antagonist BQ-123 (1 mg/kg), while the ETB receptor antagonist BQ-788 (3 mg/kg) had no effect. In conclusion, ET-1 acting via ETA receptors produces reversal of haemorrhagic hypotension in rats due to the mobilisation of blood from venous reservoirs, with the improvements in cardiac function and the perfusion of peripheral tissues.     

Systemic hemodynamics and renal function in hemorrhaged dogs resuscitated with cross-linked hemoglobin

Cross-linked hemoglobin (XL-Hb) infused into dogs increases mean arterial pressure (MAP) but decreases blood flow to the renal (RBF), mesenteric (MBF), and iliac (IBF) circulations. These actions differ markedly from dextran infusion (which increases RBF, MBF, and IBF without altering MAP) and may be due to scavenging of nitric oxide by XL-Hb. However, because the hormonal milieu regulating regional circulation is altered during hemorrhage (when XL-Hb may be used), we studied whether systemic hemodynamics, RBF, MBF, IBF, and renal excretory function in hemorrhaged dogs was altered when resuscitated with XL-Hb compared with dextran (n = 6 each). Hemorrhage decreased MAP by 25% due to a 75% decline in cardiac output. RBF, MBF, and IBF all fell by 33, 64, and 72%, respectively (P<0.05 each). There was also a fall in glomerular filtration rate (GFR), urinary flow, and sodium excretion (P<0.05 each). After resuscitation, MAP, cardiac output, RBF, MBF, IBF, and GFR all recovered to basal values with either XL-Hb or dextran. Urinary flow and sodium excretion increased to above basal levels with dextran (both by 3.5-fold; P<0.05) or XL-Hb (by 7.5- and 10-fold, respectively; P<0.05). We conclude that resuscitation with XL-Hb after hemorrhage not only increases MAP, but also restores RBF, MBF, IBF, GFR, and urinary sodium and volume excretion analogously to dextran. The results contrast with those in normal dogs and suggest that nitric oxide inhibition does not impair hemodynamic and renal function recovery during hemorrhage.     

Hemodynamic and renal effects of acute and progressive nitric oxide synthesis inhibition in anesthetized dogs

This study evaluated the effects of progressive nitric oxide (NO) inhibition in the regulation of systemic and regional hemodynamics and renal function in anesthetized dogs. The N(G)-nitro-L-arginine methyl ester group (n = 9) received progressive doses of 0.1, 1, 10, and 50 microg. kg(-1). min(-1). Renal (RBF), mesenteric (MBF), iliac (IBF) blood flows, mean arterial pressure (MAP), pulmonary pressures, cardiac output (CO), and systemic and pulmonary vascular resistances were measured. During N(G)-nitro-L-arginine methyl ester infusion, MAP and systemic vascular resistances increased in a dose-dependent manner. Mean pulmonary pressure and pulmonary vascular resistances increased in both the N(G)-nitro-L-arginine methyl ester and the control group, but the increase was more marked in the N(G)-nitro-L-arginine methyl ester group during the last two infusion periods. CO decreased progressively, before any significant change in blood pressure was noticeable in the N(G)-nitro-L-arginine methyl ester group. IBF decreased significantly from the first N(G)-nitro-L-arginine methyl ester dose, whereas RBF and MBF only decreased significantly during the highest N(G)-nitro-L-arginine methyl ester dose. Urinary volume and sodium excretion only increased significantly in the time control group during the two last time periods. The pulmonary vasculature was more sensitive than the systemic vasculature, whereas skeletal muscle and renal vasculatures showed a greater sensitivity to the inhibition of NO production than the mesenteric vasculature. NO synthesis inhibition induces a progressive antidiuretic and antinatriuretic effect, which is partially offset by the increase in blood pressure.     

Comparative effects of vasopressin, norepinephrine, and L-canavanine, a selective inhibitor of inducible nitric oxide synthase, in endotoxic shock

Norepinephrine (NE), a standard of care, AVP, an alternative candidate, and L-canavanine (LC), a selective inhibitor of inducible nitric oxide synthase, were compared for efficacy and innocuousness on global and regional hemodynamics, plasmatic and tissue lactate-to-pyruvate ratio (L/P), tissue high-energy phosphates, renal function, and tissue capillary permeability in a rat model of endotoxic normokinetic shock. Mean arterial pressure (MAP) decreased ( approximately 35%) but aortic blood flow increased during endotoxin infusion (P < 0.05 vs. control). Additionally, there was a decrease in mesenteric (MBF) and renal (RBF) blood flows along with regional-to-systemic ratio (P < 0.05 vs. control). All tested drugs restored MAP to basal levels but slightly decreased abdominal aortic flow; however, RBF and MBF remained unchanged. Endotoxin significantly decreased diuresis and inulin clearance ( approximately 3- to 4-fold), whereas AVP or LC attenuated this drop (P < 0.05 vs. control). In contrast, NE did not improve endotoxin-induced renal dysfunction. Endotoxin induced gut and lung hyperpermeability (P < 0.05 vs. control). Endotoxin-induced gut hyperpermeability was inhibited by AVP, LC, and NE. Endotoxin-induced lung hyperpermeability was further worsened by NE ( approximately 2-fold increase) but not AVP infusion (P < 0.05 vs. endotoxin). LC significantly improved endotoxin-induced pulmonary hyperpermeability. Endotoxin increased renal lactate and decreased renal ATP. NE did not change renal lactate or renal ATP. AVP and LC decreased renal lactate and normalized renal ATP. Finally, endotoxin was associated with increased lactate levels and L/P ( approximately 2- and 1.5-fold increases vs. control, respectively), whereas AVP and LC, but not NE, normalized both parameters after endotoxin challenge. These results suggest that, in a short-term endotoxic shock model, AVP improves systemic hemodynamics without side effects and has particular beneficial effects on renal function.     

Role of NO and cytochrome P-450-derived eicosanoids in ET-1-induced changes in intrarenal hemodynamics in rats

Endothelin-1 (ET-1) produces potent renal effects that we have previously shown to be dependent on cytochrome P-450 (CYP450) metabolites of aracidonic acid (24) This study evaluated the role of these metabolites in the effects produced by ET-1 on renal blood flow (RBF), cortical blood flow (CBF), medullary blood flow (MBF), and mean arterial blood pressure (MBP). ET-1 (20-200 pmol/kg) increased MBP, renal vascular resistance (RVR), and MBF but reduced CBF and RBF in a dose-dependent manner. The decreases in CBF and RBF, and increases in MBP and RVR were blunted by BMS-182874, an ET(A) receptor antagonist or BQ-788, an ET(B) receptor antagonist. Similarly, indomethacin, an inhibitor of cyclooxygenase activity, or 12,12-dibromododecenoic acid (DBDD), a CYP450-dependent inhibitor of production of 20-hydroxyeicosatetraenoic acid (20-HETE), blunted these effects. ET-3 elicited dose-related reduction in CBF and increase in MBF. Indomethacin accentuated the reduction in CBF and attenuated the increase in MBF, as did DBDD. ET-1-induced increase in MBF was attenuated by BQ-788, N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, indomethacin, or DBDD. DBDD inhibited the hemodynamic effects of L-NAME. Miconazole, the inhibitor of CYP450-dependent epoxygenase activity, was without effect. These results indicate that hemodynamic changes produced by ET-1 are mediated by vasoconstrictor prostanoids and/or prostanoid-like substances, possibly, 20-HETE via activation of ET(A) and ET(B) receptors. However, the increase in MBF is mediated by vasodilator prostanoids or by NO via ET(B) receptor activation.     

Selective effect of tempol on renal medullary hemodynamics in spontaneously hypertensive rats

The present study assessed the short- and long-term effect of tempol, a membrane-permeable mimetic of superoxide dismutase, on renal medullary hemodynamics in spontaneously hypertensive rats (SHR). Tempol was given in the drinking water (1 mM) for 4 days or 7 wk (4-11 wk of age), and medullary blood flow (MBF) was measured over a wide range of renal arterial pressure by means of laser-Doppler flowmetry in anesthetized rats. In addition, the response of the medullary circulation to angiotensin II (5-50 ng x kg(-1) x min(-1) iv) was determined in SHR treated for 4 days with tempol. Compared with control SHR, short- and long-term treatment with tempol decreased arterial pressure by approximately 20 mmHg and increased MBF by 35-50% without altering total renal blood flow (RBF) or autoregulation of RBF. Angiotensin II decreased RBF and MBF dose dependently (approximately 30% at the highest dose) in control SHR. In SHR treated with tempol, angiotensin II decreased RBF (approximately 30% at the highest dose) but did not alter MBF significantly. These data indicate that the antihypertensive effect of short- and long-term administration of tempol in SHR is associated with a selective increase in MBF. Tempol also reduced the sensitivity of MBF to angiotensin II. Taken together, these data support the idea that tempol enhances vasodilator mechanisms of the medullary circulation, possibly by interacting with the nitric oxide system. Increased MBF and reduced sensitivity of MBF to angiotensin II may contribute to the antihypertensive action of tempol in SHR.     

Centrally acting leptin induces a resuscitating effect in haemorrhagic shock in rats

Centrally acting leptin induces the activation of the sympathetic nervous system with a pressor effect in normotensive rats. The purpose of the study was to examine central leptin-evoked action in critical haemorrhagic hypotension. In anaesthetized male Wistar rats subjected for irreversible haemorrhagic shock with mean arterial pressure (MAP) 20-25 mmHg haemodynamic parameters and plasma concentrations of adrenaline and noradrenaline were measured. Leptin given intracerebroventricularly (20 μg) evoked long-lasting rises in MAP and heart rate (HR), with a subsequent increase in renal, mesenteric and hindquarters blood flows and a 100% survival at 2 h. MAP and peripheral blood flow changes were inhibited by a pre-treatment with α(1)- and α(2)-adrenoceptor antagonists prazosin (0.5 mg/kg) and yohimbine (1 mg/kg), while β-adrenoceptor antagonist propranolol (1 mg/kg) blocked leptin-induced HR changes, without influence on MAP, peripheral blood flows and survival. Twenty min after leptin treatment, there were higher plasma concentrations of noradrenaline, but not adrenaline, in comparison with the saline-treated control group. In conclusion, centrally acting leptin induces a long-lasting pressor effect with an improvement in the survival rate in haemorrhage-shocked rats. The effect may be associated with the activation of the sympathetic nervous system.     

Differential neural control of intrarenal blood flow

To test whether renal sympathetic nerve activity (RSNA) can differentially regulate blood flow in the renal medulla (MBF) and cortex (CBF) of pentobarbital sodium-anesthetized rabbits, we electrically stimulated the renal nerves while recording total renal blood flow (RBF), CBF, and MBF. Three stimulation sequences were applied 1) varying amplitude (0.5-8 V), 2) varying frequency (0.5-8 Hz), and 3) a modulated sinusoidal pattern of varying frequency (0. 04-0.72 Hz). Increasing amplitude or frequency of stimulation progressively decreased all flow variables. RBF and CBF responded similarly, but MBF responded less. For example, 0.5-V stimulation decreased CBF by 20 +/- 9%, but MBF fell by only 4 +/- 6%. The amplitude of oscillations in all flow variables was progressively reduced as the frequency of sinusoidal stimulation was increased. An increased amplitude of oscillation was observed at 0.12 and 0.32 Hz in MBF and to a lesser extent RBF, but not CBF. MBF therefore appears to be less sensitive than CBF to the magnitude of RSNA, but it is more able to respond to these higher frequencies of neural stimulation.     

Cardiovascular effects of histamine administered intracerebroventricularly in critical haemorrhagic hypotension in rats.

The study was designed to determine the cardiovascular effects of histamine administered intracerebroventricularly (icv) in a rat model of volume-controlled haemorrhagic shock. The withdrawal of approximately 50% of total blood volume resulted in the death of all control saline icv treated animals within 30 min. Icv injection of histamine produced a prompt dose-dependent (0.1-100 nmol) and long-lasting (10-100 nmol) increase in mean arterial pressure (MAP), pulse pressure (PP) and heart rate (HR), with a 100% survival of 2h after treatment (100 nmol). The increase in MAP and HR after histamine administration in bled rats in comparison to the normovolaemic animals was 2.7-3.3- and 1.3-3.6-fold higher, respectively. Pretreatment with chlorpheniramine (50 nmol icv), H1 receptor antagonist, inhibited the increase in MAP, PP, HR and survival rate produced by histamine, while chlorpheniramine given alone had no effect. Neither ranitidine (50 nmol icv), H2 histamine receptor antagonist, nor thioperamide (50 nmol icv), H3 receptor blocker, influenced the histamine action, however, when given alone, both evoked the pressor effect with elongation of survival time. It can be concluded that histamine administered icv reverses the haemorrhagic shock conditions, and histamine H1 receptors are involved.     

Angiotensin II and nitric oxide in neural control of intrarenal blood flow

We investigated the roles of the renin-angiotensin system and the significance of interactions between angiotensin II and nitric oxide, in responses of regional kidney perfusion to electrical renal nerve stimulation (RNS) in pentobarbital sodium-anesthetized rabbits. Under control conditions, RNS (0.5-8 Hz) reduced total renal blood flow (RBF; -89 +/- 3% at 8 Hz) and cortical perfusion (CBF; -90 +/- 2% at 8 Hz) more than medullary perfusion (MBF; -55 +/- 5% at 8 Hz). Angiotensin II type 1 (AT(1))-receptor antagonism (candesartan) blunted RNS-induced reductions in RBF (P = 0.03), CBF (P = 0.007), and MBF (P = 0.04), particularly at 4 and 8 Hz. Nitric oxide synthase inhibition with N(G)-nitro-L-arginine (L-NNA) enhanced RBF (P = 0.003), CBF (P = 0.001), and MBF (P = 0.03) responses to RNS, particularly at frequencies of 2 Hz and less. After candesartan pretreatment, L-NNA significantly enhanced RNS-induced reductions in RBF (P = 0.04) and CBF (P = 0.007) but not MBF (P = 0.66). Renal arterial infusion of angiotensin II (5 ng.kg(-1).min(-1)) selectively enhanced responses of MBF to RNS in L-NNA-pretreated but not in vehicle-pretreated rabbits. In contrast, greater doses of angiotensin II (5-15 ng.kg(-1).min(-1)) blunted responses of MBF to RNS in rabbits with intact nitric oxide synthase. These results suggest that endogenous angiotensin II enhances, whereas nitric oxide blunts, neurally mediated vasoconstriction in the renal cortical and medullary circulations. In the renal medulla, but not the cortex, angiotensin II also appears to be able to blunt neurally mediated vasoconstriction.     

Effect of cardiac receptor stimulation on renal vascular resistance in the pregnant rat

Stimulation of cardiac receptors (CR) evokes blunted reflex reductions in mean arterial pressure (MAP) in pregnant compared with virgin rats. Because CR-mediated sympathoinhibition has preferential effects on the kidney, we tested whether, during pregnancy, renal vascular resistance (RVR) changes less in response to CR stimulation and investigated possible mechanisms. MAP, right atrial pressure, renal sympathetic nerve activity (RSNA), renal blood flow (RBF), and RVR were measured in anesthetized animals in response to CR stimulation by graded atrial injections of saline. Baseline MAP and RVR and reflex changes in these variables during CR stimulation were reduced in late-pregnant vs. virgin rats (P<0.05). Reflex changes in RSNA were attenuated in pregnant rats, but changes in RBF as a function of RSNA were similar in both groups. ANG II AT(1)-receptor blockade increased basal RBF more in virgin rats (P<0.05), but between-group differences in reflex changes in MAP, RSNA, and RVR were maintained after AT(1) blockade. Thus during CR simulation, reflex changes in RVR were reduced in pregnant versus virgin rats. This difference does not appear to involve differential effects of ANG II.     

胍丁胺对Dahl盐敏感型高血压大鼠和Dahl盐抵抗型大鼠血流动力学的影响

在麻醉Dahl盐敏感型(DS)高血压大鼠和Dahl盐抵抗型(DR)正常血压大鼠,研究了静注胍丁胺(agmatine,AGM)对血流动力学的影响.结果显示(1)静注AGM(1,10,20mg/kg)可剂量依赖性地降低DS和DR大鼠的HR,MAP,LVP,±LVdp/dtmax,CI和TPRI.在DS高血压大鼠,MAP,LVP,±LVdp/dtmax和TPRI较DR正常血压大鼠下降幅度要大;而HR和CI在两种大鼠下降幅度无差异.需特别提出的是,DS高血压大鼠在静注高剂量AGM(20mg/kg)后,各项血流动力学指标出现先降低而后升高的现象,这一结果在DR正常血压大鼠并未出现.(2)预先静注咪唑啉受体(IR)和α2-肾上腺素能受体阻断剂(α2-AR)idazoxan(2.5mg/kg)可部分阻抑AGM的血流动力学效应.(3)预先静注α2-肾上腺素能受体阻断剂yohimbine(4mg/kg)同样可部分阻抑AGM的效应.(4)预先静注咪唑啉受体(I1)和α2-肾上腺素能受体阻断剂efaroxan(2.5mg/kg)则完全阻断AGM的血流动力学效应.以上结果表明,AGM可显著降低麻醉DR和DS大鼠的HR,MAP,LVP,±LVdp/dtmax,CI和TPRI;此效应似主要由I1-IR所介导,并有I2-IR和α2-AR参与.     

Renal tissue NO and intrarenal haemodynamics during experimental variations of NO content in anaesthetised rats.

Direct renal nitric oxide (NO) measurements were infrequent and no simultaneous measurements of renal cortical and medullary NO and local perfusion. Large-surface NO electrodes were placed in renal cortex and medulla of anaesthetised rats; simultaneously, renal blood flow (RBF, index of cortical perfusion) and medullary laser-Doppler flux (MBF) were determined. NO synthase inhibitors: nonselective (L-NAME) or selective for neuronal NOS (nNOS) (S-methyl-thiocitrulline, SMTC), and NO donor (SNAP), were used to manipulate tissue NO. Baseline tissue NO was significantly higher in medulla (703+/-49 NM) than in cortex (231+/-17 nM). Minimal cortical and medullary NO current measured after maximal L-NAME dose (2.4 mg kg(-1) i.v.) was taken as tissue NO zero kevel. This dose decreased RBF and MBF significantly (-43%). SMTC, 1.2 mg kg(-1) h(-1) i.v., significantly decreased tissue NO by 105+/-32 nM in cortex and 546+/-64 nM in medulla, RBF and MBF decreased 30% and 20%, respectively. Renal artery infusion of SNAP, 0.24 mg kg(-1) min(-1) significantly increased tissue NO by 139+/-18 nM in cortex and 948+/-110 nM in medulla. Since inhibition of nNOS decreased medullary NO by 80% and MBF by 20% only, this isoform has probably minor role in the maintenance of medullary perfusion.     

The vasoactive effects of captopril (SQ 14225). Preliminary research

The Authors examined the behaviour of the humeral arterial pressure, of the heart frequency and of the muscular blood flow in inferior limbs. This study was performed before and after treatment with Captopril (SQ 14225), 100 mg per os, a selective inhibitor of the converting enzyme. Both resting blood flow (RBF) and maximal blood flow (NBF) were studied by Xenon 133 clearance. The A.A. observed that the drug induced a significant (P less than 0.01) increase of both RBF and MBF. Therefore, the Authors hypothesize that the Captopril is able to produce peripheral vasodilatation, without any significant variation of the cardiac index and frequency. Such an effect is considered to depend not only upon the inhibited angiotensin II production, but also upon stimulation of bradikinins and prostaglandins.     

Plasma lactate concentration and muscle blood flow during dynamic exercise with negative-pressure breathing.

This study assessed the hypothesis that increasing cardiac filling pressure (CFP) would enhance contracting muscle blood flow (MBF) by stretching cardiopulmonary baroreceptors and attenuate the increase in plasma lactate concentration ([Lac(-)](p)) during dynamic exercise. Continuous negative-pressure breathing (CNPB) (-15 cmH(2)O) was used to increase the CFP by accelerating the venous return to the heart. In the first series of experiments, 10 men performed a graded exercise seated on a cycle ergometer with (N1) and without CNPB (C1). The increase in [Lac(-)](p) for N1 was attenuated at 60%, 90%, and 100% of maximal exercise intensity compared with that in C1 (P < 0.001). Also, the increases in mean arterial pressure (MAP) and plasma catecholamine concentrations were attenuated in N1 compared with those in C1 throughout the graded exercise (P < 0.05). However, heart rate and pulse pressure were not significantly influenced by CNPB. Second, we studied the impact of CNPB on forearm MBF during a rhythmic handgrip exercise in 5 of the 10 subjects. Forearm MBF was measured immediately after cessation of the exercise by venous occlusion plethysmography at rest, 30%, 50%, and 70% of maximal work load (WL(max)) with (N2) and without CNPB (C2). Forearm MBF and vascular conductance for both trials increased with the increase in intensity, but forearm skin blood flow measured by laser-Doppler flowmetry remained unchanged. MBF and vascular conductance in N2, however, increased more than in C2 at every intensity (P < 0.01) except for MBF at 70% WL(max), whereas the increase in MAP for N2 was attenuated compared with that in C2 (P < 0.05). Thus augmented active muscle vasodilation occurred in N2 with a lower increase in MAP compared with that in C2. These findings suggest that the stretch of intrathoracic baroreceptors, such as cardiopulmonary mechanoreceptors, by CNPB increased MBF by suppressing sympathetic nerve activity. The attenuation of the increase in [Lac(-)](p) might be caused, at least partially, by the increased MBF.     

Treatment of the inadequate endometrium in infertility

The one feature that characterizes all shock, regardless of its cause, is a reduction in the effective circulating blood volume. The reduced blood volume leads to decreased venous return, decreased cardiac output, vasoconstriction, tachycardia, hypotension, tissue anoxia and death if the sequence of events is uninterrupted. Immediate therapy must be directed at restoration of the blood volume, preferably with whole blood. Infection must be controlled by use of antibiotics intramuscularly and intravenously. If shock persists, aqueous adrenal extract should be administered in large quantities. As a last resort, a vasopressor should be tried.     

ANG II type 2 receptors and neural control of intrarenal blood flow

We tested the hypothesis that activation of angiotensin type 2 (AT(2)) receptors, by both exogenous and endogenous ANG II, modulates neurally mediated vasoconstriction in the renal cortical and medullary circulations. Under control conditions in pentobarbital-anesthetized rabbits, electrical stimulation of the renal nerves (RNS; 0.5-8 Hz) reduced renal blood flow (RBF; -88 +/- 3% at 8 Hz) and cortical perfusion (CBF; -92 +/- 2% at 8 Hz) more than medullary perfusion (MBF; -67 +/- 6% at 8 Hz). Renal arterial infusion of ANG II, at a dose titrated to reduce RBF by approximately 40-50% (5-50 ng.kg(-1).min(-1)) blunted responses of MBF to RNS, without significantly affecting responses of RBF or CBF. Subsequent administration of PD123319 (1 mg/kg plus 1 mg.kg(-1).h(-1)) during continued renal arterial infusion of ANG II did not significantly affect responses of RBF or CBF to RNS but enhanced responses of MBF, so that they were similar to those observed under control conditions. In contrast, administration of PD123319 alone blunted responses of CBF and MBF to RNS. Subsequent renal arterial infusion of ANG II in PD123319-pretreated rabbits restored CBF responses to RNS back to control levels. In contrast, ANG II infusion in PD123319-pretreated rabbits did not alter MBF responses to RNS. These data indicate that exogenous ANG II can blunt neurally mediated vasoconstriction in the medullary circulation through activation of AT(2) receptors. However, AT(2)-receptor activation by endogenous ANG II appears to enhance neurally mediated vasoconstriction in both the cortical and medullary circulations.     

Intrarenal infusion of bradykinin elicits a pressor response in conscious rats via a B2-receptor mechanism.

Bradykinin (BK) is a peptide known to activate afferent nerve fibers from the kidney and elicit reflex changes in the cardiovascular system. The present study was specifically designed to test the hypothesis that bradykinin B2 receptors mediated the pressor responses elicited during intrarenal bradykinin administration. Pulsed Doppler flow probes were positioned around the left renal artery to measure renal blood flow (RBF). A catheter, to permit selective intrarenal administration of BK, was advanced into the proximal left renal artery. The femoral artery was cannulated to measure mean arterial pressure (MAP). MAP, heart rate (HR), and RBF were recorded from conscious unrestrained rats while five-point cumulative dose-response curves during an intrarenal infusion of BK (5-80 microg x kg(-1) x min(-1)) were constructed. Intrarenal infusion of BK elicited dose-dependent increases in MAP (maximum pressor response, 26+/-3 mmHg), accompanied by a significant tachycardia (130+/-18 beats/min) and a 28% increase in RBF. Ganglionic blockade abolished the BK-induced increases in MAP (maximum response, -6+/-5 mmHg), HR (maximum response 31+/-14 beats/min), and RBF (maximum response, 7+/-2%). Selective intrarenal B2-receptor blockade with HOE-140 (50 microg/kg intrarenal bolus) abolished the increases in MAP and HR observed during intrarenal infusion of BK (maximum MAP response, -2+/-3 mmHg; maximum HR response, 15+/-11 beats/min). Similarly, the increases in RBF were prevented after HOE-140 treatment. In fact, after HOE-140, intrarenal BK produced a significant decrease in RBF (22%) at the highest dose of BK. Results from this study show that the cardiovascular responses elicited by intrarenal BK are mediated predominantly via a B2-receptor mechanism.     

Sympathetic nerve and cardiovascular responses to chemical activation of the midbrain defense region

The changes in mean arterial pressure (MAP), renal (RBF) and femoral (FBF) blood flows, and inferior cardiac (CN) and vertebral nerve (VN) sympathetic nerve discharges (SND) produced by chemical activation (D,L-homocysteic acid) of the midbrain periaqueductal gray (PAG) were compared in baroreceptor-denervated and -innervated cats anesthetized with urethan. Defenselike cardiovascular responses in both states were similar in magnitude and consisted of increased MAP and FBF and decreased RBF; however, the nerve responses differed. In baroreceptor-denervated cats, PAG activation increased CN 10-Hz activity, decreased VN 10-Hz activity, and lengthened the CN-VN phase angle. In baroreceptor-innervated cats in which the rhythm in SND was cardiac related, PAG activation increased CN activity, but VN activity and the CN-VN phase angle were unchanged. These results demonstrate that chemical activation of PAG neurons induces differential patterns of sympathetic outflow generally consistent with accompanying defenselike cardiovascular responses. However, the mechanisms responsible for the changes in 10-Hz and cardiac-related SND appear to be different.     

Autoregulation of renal medullary blood flow in rabbits

We examined the extent of renal medullary blood flow (MBF) autoregulation in pentobarbital-anesthetized rabbits. Two methods for altering renal arterial pressure (RAP) were compared: the conventional method of graded suprarenal aortic occlusion and an extracorporeal circuit that allows RAP to be increased above systemic arterial pressure. Changes in MBF were estimated by laser-Doppler flowmetry, which appears to predominantly reflect erythrocyte velocity, rather than flow, in the kidney. We compared responses using a dual-fiber needle probe held in place by a micromanipulator, with responses from a single-fiber probe anchored to the renal capsule, to test whether RAP-induced changes in kidney volume confound medullary laser-Doppler flux (MLDF) measurements. MLDF responses were similar for both probe types and both methods for altering RAP. MLDF changed little as RAP was altered from 50 to >or=170 mmHg (24 +/- 22% change). Within the same RAP range, RBF increased by 296 +/- 48%. Urine flow and sodium excretion also increased with increasing RAP. Thus pressure diuresis/natriuresis proceeds in the absence of measurable increases in medullary erythrocyte velocity estimated by laser-Doppler flowmetry. These data do not, however, exclude the possibility that MBF is increased with increasing RAP in this model, because vasa recta recruitment may occur.