Intrarenal distribution of renal blood flow in the rat.

Intrarenal blood flow distribution was studied with the simultaneous use of the 99Tc labelled frog erythrocyte (microsphere) and the radioactive 86Rb fractionation method in the rat. The amount of blood entering the outer cortex (99Tc labelled erythrocytes method) proved to be higher than one perfusing the outer cortex (86Rb method), whereas the amount of blood entering the inner cortex (99Tc method) was less than the amount perfusing the inner cortex and medulla (86Rb method). Hence a group of the preglomerular arterioles in the outer cortex contributes to the blood supply of the inner cortex, on the other hand a group of preglomerular arteries in the inner cortex participates in the postglomerular blood supply of the medulla. Changes in the renal circulation are, however, associated with altered distribution of postglomerular vascular segments supplied by some groups of preglomerular arterioles. From this it is concluded that the postglomerular vessels of the deeper cortical layers constitute a system which is not parallelly coupled but comprises both series- and parallel-coupled sections. The contribution of these sections appears to vary depending on the actual haemodynamic conditions.     

Hemodynamic interactions between intrinsic blood flow control mechanisms in the rat kidney

In order to reconcile the controversial concepts of myogenically and tubuloglomerular-feedback (TGF)-mediated control of renal vascular resistance, a hypothesis is advanced according to which both mechanisms interact hemodynamically because of their serial arrangement. Whereas the myogenic mechanism is suggested to be localized in the more upstream segments of the preglomerular resistance vessels, the TGF mechanism is assumed to control the pre- and/or postglomerular vascular segment(s), close to the glomerular vascular pole. The efferent vascular resistance, however, is assumed to function generally akin to a 'passive' flow resistor. These assumptions together with elementary hemodynamic considerations, allow formulation of a simple renal hemodynamic model whose quantitative predications regarding the characteristics of RBF, GFR and TGF control are remarkably consistent with the literature: (1) the magnitude of TGF response is mainly dependent upon the myogenic cooperative amplification and (2) although the TGF mechanism is not involved in the autoregulative control of RBF and GFR, changes of the TGF function may shift the autoregulation curve to higher or lower RBF and blood pressure levels.     

Impaired blood flow autoregulation in nonfiltering kidneys: effects of theophylline administration

To investigate blood flow autoregulation in filtering and nonfiltering kidneys, renal blood flow was determined during graded reductions in renal perfusion pressure in seven anesthetized dogs containing both a filtering and nonfiltering kidney. In each dog, one kidney was made nonfiltering by the method of EH Blaine, JO Davis, and RT Witty (Circ Res 27:1081-1089, 1970). Renal perfusion pressure was decreased from 129 to 115, 99, and 83 mm Hg by stepwise constriction of the suprarenal aorta. In filtering kidneys, the maximum decrease in renal perfusion pressure reduced renal blood flow only 20.1% of control whereas renal blood flow of nonfiltering kidneys decreased by 41.0% of control. During aortic constriction, renal vascular resistance of nonfiltering kidneys remained unchanged or slightly increased. These hemodynamic changes were associated with significantly greater autoregulation indices in nonfiltering kidneys. In eight dogs with nonfiltering kidneys, competitive inhibition of adenosine with theophylline (9 mg/kg iv) restored autoregulation of renal blood flow as shown by significant decreases in renal vascular resistance. These data indicate that in the nonfiltering kidney model, autoregulation of renal blood flow is impaired. It is suggested that this impaired autoregulatory response may result from renal ischemia and the vasoconstrictor influence of elevated intrarenal adenosine concentration.     

ANG II-induced downregulation of RBF after a prolonged reduction of renal perfusion pressure is due to pre- and postglomerular constriction

Previous experiments from our laboratory showed that longer-lasting reductions in renal perfusion pressure (RPP) are associated with a gradual decrease in renal blood flow (RBF) that can be abolished by clamping plasma ANG II concentration ([ANG II]). The aim of the present study was to investigate the mechanisms behind the RBF downregulation in halothane-anesthetized Sprague-Dawley rats during a 30-min reduction in RPP to 88 mmHg. During the 30 min of reduced RPP we also measured glomerular filtration rate (GFR), proximal tubular pressure (P(prox)), and proximal tubular flow rate (Q(LP)). Early distal tubular fluid conductivity was measured as an estimate of early distal [NaCl] ([NaCl](ED)), and changes in plasma renin concentration (PRC) over time were measured. During 30 min of reduced RPP, RBF decreased gradually from 6.5 +/- 0.3 to 6.0 +/- 0.3 ml/min after 5 min (NS) to 5.2 +/- 0.2 ml/min after 30 min (P < 0.05). This decrease occurred in parallel with a gradual increase in PRC from 38.2 +/- 11.0 x 10(-5) to 87.1 +/- 25.1 x 10(-5) Goldblatt units (GU)/ml after 5 min (P < 0.05) to 158.5 +/- 42.9 x 10(-5) GU/ml after 30 min (P < 0.01). GFR, P(prox), and [NaCl](ED) all decreased significantly after 5 min and remained low. Estimates of pre- and postglomerular resistances showed that the autoregulatory mechanisms initially dilated preglomerular vessels to maintain RBF and GFR. However, after 30 min of reduced RPP, both pre- and postglomerular resistance had increased. We conclude that the decrease in RBF over time is caused by increases in both pre- and postglomerular resistance due to rising plasma renin and ANG II concentrations.     

A perinatal nitric oxide donor increases renal vascular resistance and ameliorates hypertension and glomerular injury in adult fawn-hooded hypertensive rats

Enhancing perinatal nitric oxide (NO) availability persistently reduces blood pressure in spontaneously hypertensive rats. We hypothesize that this approach can be generalized to other models of genetic hypertension, for instance those associated with renal injury. Perinatal exposure to the NO donor molsidomine was studied in fawn-hooded hypertensive (FHH) rats, a model of mild hypertension, impaired preglomerular resistance, and progressive renal injury. Perinatal molsidomine increased urinary NO metabolite excretion at 8 wk of age, i.e., 4 wk after treatment was stopped (P < 0.05). Systolic blood pressure was persistently reduced after molsidomine (42-wk females: 118 +/- 3 vs. 141 +/- 5 and 36-wk males: 139 +/- 4 vs. 158 +/- 4 mmHg; both P < 0.001). Perinatal treatment decreased glomerular filtration rate (P < 0.05) and renal blood flow (P < 0.01) and increased renal vascular resistance (P < 0.05), without affecting filtration fraction, suggesting persistently increased preglomerular resistance. At 4 wk of age natriuresis was transiently increased by molsidomine (P < 0.05). Molsidomine decreased glomerulosclerosis (P < 0.05). Renal blood flow correlated positively with glomerulosclerosis in control (P < 0.001) but not in perinatally treated FHH rats. NO dependency of renal vascular resistance was increased by perinatal molsidomine. Perinatal enhancement of NO availability can ameliorate development of hypertension and renal injury in FHH rats. Paradoxically, glomerular protection by perinatal exposure to the NO donor molsidomine may be due to persistently increased preglomerular resistance. The mechanisms by which increased perinatal NO availability can persistently reprogram kidney function and ameliorate hypertension deserve further study.     

Predominant postglomerular vascular resistance response to reflex renal sympathetic nerve activation during ANG II clamp in rabbits

We have shown previously that a moderate reflex increase in renal sympathetic nerve activity (RSNA) elevated glomerular capillary pressure, whereas a more severe increase in RSNA decreased glomerular capillary pressure. This suggested that the nerves innervating the glomerular afferent and efferent arterioles could be selectively activated, allowing differential control of glomerular capillary pressure. A caveat to this conclusion was that intrarenal actions of neurally stimulated ANG II might have contributed to the increase in postglomerular resistance. This has now been investigated. Anesthetized rabbits were prepared for renal micropuncture and RSNA recording. One group (ANG II clamp) received an infusion of an angiotensin-converting enzyme inhibitor (enalaprilat, 2 mg/kg bolus plus 2 mg.kg(-1).h(-1)) plus ANG II ( approximately 20 ng.kg(-1).min(-1)), the other vehicle. Measurements were made before (room air) and during 14% O(2). Renal blood flow decreased less during ANG II clamp compared with vehicle [9 +/- 1% vs. 20 +/- 4%, interaction term (P(GT)) < 0.05], despite a similar increase in RSNA in response to 14% O(2) in the two groups. Arterial pressure and glomerular filtration rate were unaffected by 14% O(2) in both groups. Glomerular capillary pressure increased from 33 +/- 1 to 37 +/- 1 mmHg during ANG II clamp and from 33 +/- 2 to 35 +/- 1 mmHg in the vehicle group before and during 14% O(2), respectively (P(GT) < 0.05). During ANG II clamp, postglomerular vascular resistance was still increased in response to RSNA during 14% O(2), demonstrating that the action of the renal nerves on the postglomerular vasculature was independent of the renin-angiotensin system. This further supports our hypothesis that increases in RSNA can selectively control pre- and postglomerular vascular resistance and therefore glomerular ultrafiltration.     

Baroreceptor control of pressure-flow relationships during hypoxemia

In the absence of peripheral chemoreceptors, the effects of graded hypoxemia on the carotid sinus control of central and regional hemodynamics were studied in anesthetized mongrel dogs. Baroreceptor stimulation was effected by carotid sinus isolation and perfusion under controlled pressure. Blood flows were measured in the aorta and the celiac, mesenteric, left renal, and right iliac arteries. Carotid sinus reflex set-point pressures were well maintained until hypoxemia was severe. Carotid sinus reflex set-point gain was maximal during mild hypoxemia. Reflex operating point regional flows were unaffected by hypoxemia. A factorial analysis of overall reflex increases in mean aortic pressure, flow, and power during reduced baroreceptor stimulation showed potentiation by increasing hypoxemia. Corresponding effects of baroreceptor stimulation and hypoxemia on aortic resistance and heart rate were additive. Celiac, renal, and iliac blood flows increased during both hypoxemia and reduced baroreceptor stimulation. Only in the celiac bed were blood flow changes independent of concomitant changes in cardiac output. Thus, at maximum sympathetic stimulation (low carotid sinus pressure) during hypoxemia, the cardiovascular system maintained both central and regional blood flows at high systemic blood pressures independent of the peripheral chemoreceptors.     

Canine renal vascular response to bilateral carotid occlusion during hypoxia

Chloralose-urethane anesthetized dogs were utilized to determine if hypoxemic potentiation of the baroreceptor-mediated increase in renal sympathetic nerve activity (RSNA) results in sufficient renal vascular vasoconstriction to reduce renal blood flow (RBF) during bilateral carotid occlusion (BCO). Additionally, hypercapnia and mechanical ventilation were randomly combined with hypoxemia during BCO to determine if further augmentation of renal vasoconstriction could be accomplished. BCO resulted in a similar increase in blood pressure (renal perfusion pressure) in all periods. RBF was not reduced significantly by BCO during any period even though renal vascular resistance was significantly increased by BCO during each period. When hypoxemia was combined with hypercapnia and mechanical ventilation simultaneously, there was a greater percentage increase in renal resistance with BCO. During BCO, when renal perfusion pressure was returned to control values by suprarenal aortic constriction, RBF remained unchanged and renal resistance decreased to control values. These results indicate that the BCO-induced increase in RSNA is relatively moderate and, even when potentiated by hypoxemia, hypercapnia, and mechanical ventilation, is not sufficient to reduce RBF in the presence of an increase in blood pressure and renal autoregulation.     

Intrarenal blood flow distribution: effect of carotid occlusion.

In this study we have examined the influence of bilateral carotid occlusion on intrarenal blood flow distribution. Using labeled microspheres to determine intrarenal hemodynamics, bilateral carotid ligation in mannitol or saline expanded dogs resulted in an increase in outer cortical blood flow and a decrease in inner cortical flow. Total renal blood flow and glomerular filtration rate did not change significantly during carotid occlusion whereas the average mean arterial blood pressure rose from 130 to 166 mmHg. Inner cortical flow resistance increased substantially after carotid occlusion; outer cortical resistance was unchanged. These results suggest that bilateral carotid occlusion selectively activates inner cortical renal sympathetic fibers.     

Innervation of the renal vasculature of the toad (Bufo marinus)

The innervation of the dorsal aorta and renal vasculature in the toad (Bufo marinus) has been studied with both fluorescence and ultrastructural histochemistry. The innervation consists primarily of a dense plexus of adrenergic nerves associated with all levels of the preglomerular vasculature. Non-adrenergic nerves are occasionally found in the renal artery, and even more rarely near the afferent arterioles. Many of the adrenergic nerve profiles in the dorsal aorta and renal vasculature are distinguished by high proportions of chromaffin-negative, large, filled vesicles. Close neuromuscular contacts are common in both the renal arteries and afferent arterioles. Possibly every smooth muscle cell in the afferent arterioles is multiply innervated. The glomerular capillaries and peritubular vessels are not innervated, and only 3-5% of efferent arterioles are accompanied by single adrenergic nerve fibres. Thus, nervous control of glomerular blood flow must be exerted primarily by adrenergic nerves acting on the preglomerular vasculature. The adrenergic innervation of the renal portal veins and efferent renal veins may play a role in regulating peritubular blood flow. In addition, glomerular and postglomerular control of renal blood flow could be achieved by circulating agents acting via contractile elements in the glomerular mesangial cells, and in the endothelial cells and pericytes of the efferent arterioles. Some adrenergic nerve profiles near afferent arterioles are as close as 70 nm to distal tubule cells, indicating that tubular function may be directly controlled by adrenergic nerves.     

Chemical activation of thin-fiber phrenic afferents. 2. Cardiovascular responses

To assess the effects of groups III and IV (thin-fiber) phrenic afferents on arterial pressure, heart rate, and distribution of cardiac output, we injected capsaicin into phrenic arteries of in situ isolated and innervated left diaphragms of dogs anesthetized with chloralose, vagotomized, and mechanically ventilated. Blood flow in the ascending aorta, common carotid, renal, superior mesenteric, and femoral arteries was measured by electromagnetic and Doppler flow probes. Injection of 1 mg capsaicin into the left phrenic artery produced congruent to 15% increase in mean arterial pressure and congruent to 7% increase in heart rate with no change in aortic flow. Phrenic arterial flow decreased by 64%, renal arterial flow by 16%, and superior mesenteric arterial flow by 10%, whereas carotid flow increased by 13% and flow to the right gastrocnemius muscle did not change. Mean arterial pressure, heart rate, and blood flow distribution (with the exception of the decline in phrenic blood flow) returned to baseline within 60 s of the injection. Injection of 1.5 mg capsaicin into the right isolated and innervated gastrocnemius produced congruent to 35% increase in mean arterial pressure, 17% rise in heart rate, and no change in aortic blood flow. Phrenic and carotid arterial flow rose by 240 and 41%, respectively, whereas renal and superior mesenteric flow declined by 50 and 20%, respectively. In conclusion, thin-fiber phrenic afferents have an excitatory effect on arterial pressure and heart rate. They redistribute blood flow away from the renal and intestinal vascular beds and toward the carotid vascular bed. On the other hand, the cardiovascular reflex from thin-fiber phrenic afferents seems less potent than that from limb muscle afferents.     

Cardiovascular function in anesthetized miniature swine.

Miniature swine anesthetized with pentobarbital were studied with respect to their cardiovascular function under control conditions and in response to catecholamines, baroreceptor inhibition, bilateral vagotomy and vagal nerve stimulation. Measurements included aortic pressure, heart rate, intraventricular pressure and its maximum rate of rise during contraction, carotid blood flow and resistance, femoral blood flow and resistance, and renal blood flow and resistance. The cardiovascular actions of norepinephrine, epiniphrine and isoproterenol were similar to those in other mammals, and the adrenergic receptor mechanisms also were susceptible to blockade with phentolamine or propranolol. Inhibition of the carotid baroreceptors was accompanied by elevation of aortic pressure, reflex bradycardia and increased femoral and renal resistances. Bileteral vagotomy was followed by hypertension, tachycardia and increased renal resistance. Changes in femoral resistance to these procedures differed between the two strains of miniature swine studied. Stimulation of the peripheral end of either vagus nerve was accompanied by bradycardia without hypotension.     

Cardiovascular responses to V1-vasopressinergic antagonism in conscious versus anesthetized rats

Experiments were performed to compare the possible effect of endogenous arginine vasopressin on renal hemodynamics between anesthetized, surgically stressed rats and conscious rats. Animals were instrumented with arterial and venous catheters as well as with a pulsed Doppler flow probe on the left renal artery. The rats were studied under the following conditions: (1) conscious and unrestrained; (2) anesthetized only; (3) anesthetized with minor surgical stress; and (4) anesthetized with major surgical stress. Two anesthetic agents were also compared, a mixture of ketamine (110 mg/kg i.m.) and acepromazine (1 mg/kg i.m.), and sodium pentobarbital (50 mg/kg i.p.). Baseline mean arterial blood pressure was significantly higher in pentobarbital-anesthetized rats following surgical stress compared with conscious animals, but blood pressure was not affected by ketamine-acepromazine anesthesia. After baseline measurements of blood pressure, heart rate, and renal blood flow, a specific V1-vasopressinergic antagonist (d(CH2)5Tyr(Me) arginine vasopressin, 10 mg/kg i.v.) was administered to each group. Mean arterial blood pressure, heart rate, and renal blood flow were monitored for an additional 15 min. Mean arterial blood pressure and renal blood flow decreased after V1 antagonism in ketamine-acepromazine-anesthetized rats with major surgical stress, but were not affected in pentobarbital-anesthetized animals. Heart rate and renal vascular resistance were not affected following V1 blockade with either anesthetic agent. These data suggest that arginine vasopressin plays a role in maintaining blood pressure and renal perfusion in ketamine-acepromazine-anesthetized rats following surgical stress, but does not have a significant effect on renal hemodynamics under pentobarbital anesthesia.     

Aortic blood flow subtraction: an alternative method for measuring total renal blood flow in conscious dogs

We have measured total renal blood flow (TRBF) as the difference between signals from ultrasound flow probes implanted around the aorta above and below the renal arteries. The repeatability of the method was investigated by repeated, continuous infusions of angiotensin II and endothelin-1 seven times over 8 wk in the same dog. Angiotensin II decreased TRBF (350 +/- 16 to 299 +/- 15 ml/min), an effect completely blocked by candesartan (TRBF 377 +/- 17 ml/min). Subsequent endothelin-1 infusion reduced TRBF to 268 +/- 20 ml/min. Bilateral carotid occlusion (8 sessions in 3 dogs) increased arterial blood pressure by 49% and decreased TRBF by 12%, providing an increase in renal vascular resistance of 69%. Dynamic analysis showed autoregulation of renal blood flow in the frequency range <0.06-0.07 Hz, with a peak in the transfer function at 0.03 Hz. It is concluded that continuous measurement of TRBF by aortic blood flow subtraction is a practical and reliable method that allows direct comparison of excretory function and renal blood flow from two kidneys. The method also allows direct comparison between TRBF and flow in the caudal aorta.     

应用植入式遥测技术观察自发性高血压大鼠血压的昼夜波动

目的应用植入式遥测技术观察自发性高血压大鼠在清醒无束缚状态下血压昼夜波动变化。方法取8只SPF级3月龄雄性SHR大鼠,进行C50-PXT植入子植入手术,恢复7 d后,用遥测系统进行24 h连续清醒无束缚的血压监测,并用EMKA分析软件对动态血压心率均值、24 h血压心率趋势等指标进行分析。结果 3月龄的SHR大鼠血压和心律呈昼夜节律性变化,白昼阶段血压明显低于夜间阶段(P<0.01),血压在1∶30～2∶30和20∶30～21∶30时出现两个高峰期,14∶00～14∶30时出现一低谷期。其中夜间阶段平均收缩压为166.02 mmHg,两个收缩压峰值分别为172.13 mmHg和171.38 mmHg;白昼平均收缩压是162.73 mmHg,收缩压谷底值为155.73mmHg。而心率两个高峰期出现在1∶30～2∶00和20∶00～21∶00,高峰值分别为375.00次/分和373.26次/分;心率低谷出现在11∶00左右,谷底值为310.91次/分,白昼和夜间的平均心率分别为328.85次/分和346.05次/分。结论 3月龄的SHR大鼠血压和心律呈昼夜节律性变化,血压和心率在夜间出现两个高峰,白昼出现一个低谷,且夜间的平均血压和心率要高于白昼,SHR大鼠的血压和心率的节律变化与其活动有关。植入式遥测技术可准确反映SHR大鼠血压昼夜的节律性变化,有助于正确评价抗高血压药物的作用和高血压的生理机制研究。     

Extracellular volume expansion and delayed resolution of hypertension after canine aortic coarctectomy

The hemodynamic changes occuring after surgical correction of thoracic aortic coarctation were studied in two neonatally coarcted dogs at six months of age and compared to sham surgery in two littermate controls. Excision of the tight iatrogenic aortic band with direct aortic reanastomosis abolished pressure gradients. Post-coarctectomy systemic pressure rose, after an early transient fall, to pre-operative proximal levels and was sustained for two to four weeks before decreasing to control normotensive values. Femoral systolic pressure (and renal perfusion pressure) rose by 47–57 mmHg in coarcted dogs (p<.001). Extracellular volume (ECV) increased in both coarcted animals, peaking 28–32 cc/kg (7.1–7.6% increase) above precoarctectomy levels. Peak ECV expansion coincided with the peak post-coarctectomy blood pressure. Fluid administration, blood losses and plasma renin activity (PRA) were comparable in all animals. Post-coarctectomy tachycardia was also noted in coarcted dogs (p<.001), whereas neither ECV nor heart rate changes occured in control animals. We postulate that post-coarctectomy baroreceptor stimulation results in sympathetically-mediated renal sodium retention, not only preventing a pressure diuresis, but resulting in overt volume expansion. Failure of PRA suppression despite increased distal pressure and volume excess may also reflect sympathetic activation. Data are compatible with the view that sympathetic activation and consequent volume expansion transiently sustain hypertension in the post-coarctectomy setting until baroreceptor re-adjustments permits normalization of blood pressure.     

Replicability and Heterogeneity of Awake Unrestrained Canine fMRI Responses

Previously, we demonstrated the possibility of fMRI in two awake and unrestrained dogs. Here, we determined the replicability and heterogeneity of these results in an additional 11 dogs for a total of 13 subjects. Based on an anatomically placed region-of-interest, we compared the caudate response to a hand signal indicating the imminent availability of a food reward to a hand signal indicating no reward. 8 of 13 dogs had a positive differential caudate response to the signal indicating reward. The mean differential caudate response was 0.09%, which was similar to a comparable human study. These results show that canine fMRI is reliable and can be done with minimal stress to the dogs.     

The role of beta 2-adrenergic vascular receptors in the peripheral vasodilation caused by 17 beta-estradiol in anesthetized pigs

It has been previously shown in anesthetized pigs that intravenous infusion of 2 microg/h of 17beta-estradiol primarily dilated renal, iliac and coronary circulations, while higher doses of the hormone were required to cause vasodilation also in the mesenteric vascular bed. In the same experimental model, a tonic beta2-adrenoceptor mediated vasodilation, which could be argued to attenuate the vasodilator effect of 17beta-estradiol, has been described. The present study was planned to investigate the role of beta2-adrenergic receptors in the hemodynamic responses of renal and mesenteric vascular beds to 17beta-estradiol. Changes in flow caused by intravenous infusion of 2 microg/h of the hormone at constant heart rate and aortic blood pressure in the left renal and superior mesenteric arteries were assessed using electromagnetic flowmeters. In six pigs, infusion of 17beta-estradiol caused an increase in renal blood flow, which averaged 12.1% of the control values, without affecting mesenteric blood flow. In the same pigs, after hemodynamic variables had returned to the baseline values, blockade of beta2-adrenergic receptors with butoxamine caused an increase in aortic blood pressure and an increase in renal and mesenteric resistance. The subsequent infusion of 17beta-estradiol elicited increases in renal and mesenteric blood flow which respectively averaged 19.6% and 12.8%. Therefore, the present study in anesthetized pigs have shown that the vasodilator responses of the renal and mesenteric circulations to 17beta-estradiol were attenuated and even masked by a tonic beta2-adrenoceptor mediated vasodilation. This indicates that some vasodilator effects elicited by normally used replacement doses of the hormone may not be apparent.     

Renal blood flow in normal dogs and in dogs with experimental liver cirrhosis following the acute continuous infusion of endotoxin

The purpose of this study was to determine if the renal circulation of normal and cirrhotic dogs behave similarly in response to an acute endotoxin infusion. Endotoxin was administered as a slow continuous infusion (13-26 micrograms/min) to a total of 20 normal dogs through the femoral vein, portal vein, or into the left renal artery. In each case, there was an initial increment in renal blood flow, of the order of 46%, while arterial blood pressure was actually declining. After 8-20 min, blood flow fell as perfusion pressure declined further. The initial increment in renal perfusion was not due to a hyperthermic response following the endotoxin. When similar doses were given to five dogs with chronic biliary cirrhosis and ascites, the biphasic response in renal perfusion was not observed, rather blood flow declined as perfusion pressure declined. When normal dogs were infused with bilirubin, bile salts, noradrenaline, and angiotensin in pressor doses, the subsequent infusion of endotoxin still produced the usual biphasic response in renal perfusion. Chronic elevation of portal pressure (but not acute elevation), volume contraction by diuresis or hemorrhage, and the infusion of bile intravenously, all abolished the biphasic response in renal perfusion and reproduced in normal dogs the response to endotoxin observed in cirrhotic dogs. Investigation of the factors causing the initial decrease in intrarenal vascular resistance in normal dogs following the endotoxin infusion implicated a role for histamine, kinins, and prostaglandins. We conclude there is a fundamental difference in the response of the renal circulation of normal and cirrhotic dogs to an endotoxin infusion, which may depend on failure of this latter group to release one or more humoral agents. This difference may be due to elevated portal pressure, a decreased effective arterial blood volume, or the products of bile having access to the circulation in cirrhotic dogs.     

Effects of brain renin-angiotensin on cardiovascular function and saline intake in awake dogs

Initial studies were undertaken to investigate the effects of prolonged administration of angiotensin II (AII), 1 micrograms twice daily, via the lateral ventricles to mongrel dogs on arterial blood pressure and to determine if sodium intake was essential for the development of hypertension. Increasing AII levels in the cerebrospinal fluid for a prolonged period of time produced a sustained hypertensive state only in those dogs in which the daily intake of sodium was increased. The hypertension appeared to be due to an increase in total peripheral resistance. Central administration of AII increased both fluid intake and urine output. In order to assess the hemodynamic effects of increasing endogenous brain AII, renin was injected in doses of 0.025, 0.05, 0.1 and 0.3 units (from porcine kidney) into the lateral ventricles of chronically instrumented awake dogs. Hemodynamic variables were recorded prior to and one and 2 h after the central administration of renin. Renin produced a dose-dependent increase in mean arterial pressure with no significant change in heart rate or carotid, coronary and renal blood flow velocities. Chronic intraventricular administration of renin, 0.15 units twice daily to awake instrumented dogs receiving saline as the drinking fluid, markedly increased the daily intake of saline and increased diastolic and systolic blood pressure without increasing heart rate or carotid, coronary or renal blood flow velocities. There appears to be a direct significant relationship between the increase in mean blood pressure due to the intraventricular administration of renin and the volume of saline consumed.