Cardiac edema in dogs: distribution of renal blood flow and glomerular filtrate.

The injection of Freund's adjuvant into the pericardial sac of 29 dogs resulted in chronic pericardial tamponade with persistent sodium retention. Micropuncture, clearance, and radioactive microsphere experiments were initiated 6--13 days after pericardial injection and 60 min after pericardiocentesis. Pericardiocentesis increased sodium excretion (from 12.2 to 41.3 microequiv./min) and mean arterial pressure (+ 20 mmHg (1 mmHg = 133.322 Pa)). Central venous pressure decreased 6.5 mmHg, as did hematocrit (from 45.7 to 39.8%) and plasma protein concentration (from 5.88 to 5.15 g%). Pericardiocentesis had no significant effect on renal blood flow (RBF), nor plasma flow. Redistribution of glomerular filtrate was suggested by the observation that superficial nephron glomerular filtration rate increased (from 91 to 108 nL/min) while glomerular filtration rate remained unaltered. Determination of intrarenal distribution of RBF revealed that cortical blood flow also distributed superficially. A significant increase in the fraction of RBF perfusing zone 1 (outer cortex) and a decrease in fractional perfusion of zones 2, 3 and 4 (juxtamedullary cortex) were observed in each experiment following pericardiocentesis. RBF distribution examined in a series of six animals prior to and during the development of pericardial tamponade showed the opposite effect. These results indicate that pericardiocentesis causes redistribution of both glomerular filtrate and RBF to superficial nephrons. The development of pericardial tamponade was associated with increased fractional juxtamedullary blood flow. These changes may have been the result of altered blood pressure, hematocrit, plasma protein concentration, or altered renal resistance.     

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.     

Role of the renal nerves and angiotensin II in the renal function curve.

The relationship between renal perfusion pressure and urinary sodium is involved in arterial pressure regulation. The aim of this study was to investigate the role of renal nerves and angiotensin II in the pressure-natriuresis relationship. Experiments were performed in anaesthetised cats in which one kidney was surgically denervated. Renal perfusion pressure (RPP), renal blood flow (RBF) glomerular filtration rate (GFR, creatinine clearance), urinary volume (V) and sodium excretion (Una + V) were separately measured from both kidneys. RPP was progressively reduced in two consecutive steps by a suprarenal aortic snare. Two groups of animals were studied: the first without any pharmacological treatment (Untreated), the second during treatment with an angiotensin converting enzyme inhibitor (Captopril, 0.4 mg/Kg intravenously followed by an infusion of 0.4 mg/Kg/h). In the Untreated group RPP was reduced from 152.4 +/- 7.3 to 113.6 +/- 5.8 and 83.0 +/- 4.4 mmHg during the first and second step respectively. RBF and GFR were only slightly reduced during the second step of reduced RPP. In control conditions V and UNa + V were greater in the denervated compared to the innervated kidney. The graded decrease in RPP reduced both V and UNa + V in the innervated as well as in the denervated kidney. In the Captopril group V and UNa + V were larger than in the Untreated group in both the innervated and the denervated kidney. A decrease of RPP similar to that observed in the Untreated group, produced similar haemodynamic changes. Also in the Captopril group the graded decrease in RPP reduced both V and UNa + V in the innervated as well as in the denervated kidney. Matching UNa + V against RPP values significant correlations were found in the innervated and denervated kidneys of both groups. Both renal denervation and ACE inhibition were accompanied by an increased gain of the pressure-natriuresis curve, but only renal denervation shifted the crossing of the pressure axis to the left. In the ACE inhibited animals renal denervation only shifted the curve to the left. In conclusion our data suggest that i) at each level of RPP renal nerves and angiotensin II decrease renal sodium excretion, ii) renal nerves and angiotensin II increase the slope of the renal function curve, iii) renal nerves shift to the right the renal function curve.     

Renal haemodynamics in chronic unilateral ureteral obstruction in the dog

Renal blood flow and its intrarenal distribution have been investigated after 7 and 14 days of unilateral ureteral ligation (UUL) in both the ligated and the undisturbed kidney by the radioactive microsphere technique without opening the abdomen and the obstructed ureter. It has been found that renal blood flow (RBF) decreased to about 26% after 7 days and to about 10% after 14 days of normal controls in the obstructed kidney. There was a pronounced inward shifting of the much reduced RBF. The slight increase in RBF of the undisturbed kidney was not significant and did not compensate the pronounced decrease of RBF in the obstructed one.     

Dynamic relationship between sympathetic nerve activity and renal blood flow: a frequency domain approach

Blood pressure displays an oscillation at 0.1 Hz in humans that is well established to be due to oscillations in sympathetic nerve activity (SNA). However, the mechanisms that control the strength or frequency of this oscillation are poorly understood. The aim of the present study was to define the dynamic relationship between SNA and the vasculature. The sympathetic nerves to the kidney were electrically stimulated in six pentobarbital-sodium anesthetized rabbits, and the renal blood flow response was recorded. A pseudo-random binary sequence (PRBS) was applied to the renal nerves, which contains equal spectral power at frequencies in the range of interest (<1 Hz). Transfer function analysis revealed a complex system composed of low-pass filter characteristics but also with regions of constant gain. A model was developed that accounted for this relationship composed of a 2 zero/4 pole transfer function. Although the position of the poles and zeros varied among animals, the model structure was consistent. We also found the time delay between the stimulus and the RBF responses to be consistent among animals (mean 672 +/- 22 ms). We propose that the identification of the precise relationship between SNA and renal blood flow (RBF) is a fundamental and necessary step toward understanding the interaction between SNA and other physiological mediators of RBF.     

Effects of ovarian hormones on ovarian capillary blood flow in anoestrous ewes

The indicator fractionation technique with [86Rb]rubidium chloride as the indicator was used to determine the relative blood flow (RBF) as a measure of capillary blood flow in the ovaries of conscious, hormonally treated, anoestrous ewes. Treatment of ewes with either progesterone only or oestradiol only had no effect on ovarian RBF, but treatment with oestradiol subsequent to progesterone caused a significant increase (P less than 0.001). Consequently, it appears that progesterone-induced sensitivity of the ovarian vasculature to the vasodilatory effects of oestradiol may be responsible for increased ovarian blood flow around oestrus in cyclic ewes.     

Local thermodilution: a reliable technique for estimating renal blood flow in the rabbit

1. A thermistor probe designed for determination of renal blood flow in rabbits, consisted of a fast-responding bead thermistor and an injection port which was also used to measure renal venous pressure between injections. 2. By an in vitro calibration system, actual measured flow (Qa) correlates well with the thermodilution calculated flow (Qc), where Qc = 0.99 Qa + 4.9 (r = 0.97, n = 42). 3. The renal blood flow (RBF) as determined by the thermodilution technique in 3 control groups was 53 +/- 3 (8), 60 +/- 6 (8), and 62 +/- 3 (3) ml/min/kidney or about 9% of the cardiac output. 4. Hypovolemia (-10%) reduced RBF by 19% from the control value, whereas, hypervolemia (+10%) did not alter RBF. 5. Smoke-induced apnea resulted in hypertension (+30%) and bradycardia (-39%), and was associated with changes in RBF (-55%) and renal vascular resistance (+183%). 6. We conclude that the local thermodilution technique is a relatively easy and reliable method for estimating RBF in rabbits.     

Arterial spin labeling blood flow magnetic resonance imaging for evaluation of renal injury

A multitude of evidence suggests that iodinated contrast material causes nephrotoxicity; however, there have been no previous studies that use arterial spin labeling (ASL) blood flow functional magnetic resonance imaging (fMRI) to investigate the alterations in effective renal plasma flow between normointensive and hypertensive rats following injection of contrast media. We hypothesized that FAIR-SSFSE arterial spin labeling MRI may enable noninvasive and quantitative assessment of regional renal blood flow abnormalities and correlate with disease severity as assessed by histological methods. Renal blood flow (RBF) values of the cortex and medulla of rat kidneys were obtained from ASL images postprocessed at ADW4.3 workstation 0.3, 24, 48, and 72 h before and after injection of iodinated contrast media (6 ml/kg). The H&E method for morphometric measurements was used to confirm the MRI findings. The RBF values of the outer medulla were lower than those of the cortex and the inner medulla as reported previously. Iodinated contrast media treatment resulted in decreases in RBF in the outer medulla and cortex in spontaneously hypertensive rats (SHR), but only in the outer medulla in normotensive rats. The iodinated contrast agent significantly decreased the RBF value in the outer medulla and the cortex in SHR compared with normotensive rats after injection of the iodinated contrast media. Histological observations of kidney morphology were also consistent with ASL perfusion changes. These results demonstrate that the RBF value can reflect changes of renal perfusion in the cortex and medulla. ASL-MRI is a feasible and accurate method for evaluating nephrotoxic drugs-induced kidney damage.     

Fucoidan improves the renal blood flow in the early stage of renal ischemia/reperfusion injury in the rat.

It has been shown that monoclonal anti-P-selectin antibody administration protects renal function in an ischemic model of acute renal failure. This study was designed to evaluate the effect of administration of fucoidan, P-selectin inhibitor, on reduction in renal blood flow induced by ischemia/reperfusion injury in the rat. Experiments were performed on male Wistar rats weighting 35-400 g. The systemic blood pressure (mm Hg) (BP) and renal blood flow (RBF) were monitored continuously and renal vascular resistance (RVR) was calculated. After 20 min period of stabilization animals (6 rats in each group) received one of the following agents administered by continuous i.v. infusion during 165 min: 1 mg/kg of body weight of fucoidan (F1), 10 mg/kg of fucoidan (F10), 100 mg/kg of fucoidan (F100), 10 mg/kg of heparin (H), or 0.9% NaCl solution (control). After 15 min of drug administration the renal vessels of the both kidney were occluded with vascular clamps for 60 min. There were no significant changes in the initial values of RBF, RVR and BP between groups. None procedure affected significantly BP during all experiments. In F10 RBF returned to the initial values in 70th min of reperfusion and did not change up to 90th min. This value was significantly higher than respective value in the control group. In F1 group RBF in 90th min was also higher than in the control group, but it was not statistically significant. The dose of heparine and fucoidan used in the H and F100 groups failed to preserve RBF during reperfusion. In the present study we found that administration of fucoidan--P-selectin inhibitor, increases significantly postischemic renal blood flow and may have renoprotective activity.     

Effect of peritoneal rewarming on renal function in the hypothermic dog

Two groups of eight dogs were subjected to an experimentally induced hypothermia of 25 °C. One group was rewarmed externally using a circulating water blanket while the other group was rewarmed by peritoneal dialysis. Glomerular filtration rate, renal blood flow, and urine flow were reduced while filtration fraction and the extraction of PAH (E_pah) were increased during hypothermia. Immediately upon rewarming, RBF and GFR remained significantly depressed in both groups when compared to control values. By 12 hr post-rewarming, however, the group rewarmed by peritoneal dialysis showed a complete return of GFR and RBF to prehypothermic levels while in the externally rewarmed group these variables remained depressed. The data suggest that peritoneal dialysis is an effective means of core rewarming producing an earlier return of renal function to control levels that the more conventional means of external rewarming.     

Acute effects of angiotensin II on renal haemodynamics and excretion in conscious dogs

The effects of a 60-min intravenous infusion of angiotensin II (A II; 4 or 20 ng A II/min/kg body weight) on renal blood flow (RBF; electromagnetic flow transducer, control value 19-25 ml/min/kg), glomerular filtration rate (GFR; control value 4.2-5.0 ml/min/kg), mean arterial blood pressure, sodium excretion, water excretion, and plasma A II and plasma aldosterone concentrations were examined in 6 chronically instrumented female conscious beagle dogs kept on three different dietary sodium intakes (SI): SI 0.5 or SI 2.5 mmol Na/kg/day or SI 4.5 mmol Na/kg/day plus an oral saline load prior to the experiment SI 4.5(+) dogs. Four nanograms A II decreased RBF and GFR in SI 4.5(+) dogs without changing the filtration fraction (FF%); in SI 0.5 dogs the RBF decreased, and the FF% increased. Twenty nanograms A II decreased RBF and increased FF% in all dietary protocols, less in SI 4.5(+) dogs. The mean arterial blood pressure increased in all dietary protocols by 10-15 mm Hg (4 ng A II) and 32-37 mm Hg (20 ng A II). Sodium and water excretions decreased by 32 and 46%, respectively, in SI 4.5(+) dogs at both doses of A II. The plasma aldosterone concentration increased in all but one protocol: 4 ng A II, SI 4.5(+) dogs. It is concluded that when A II plasma concentrations are most likely borderline to pathophysiological conditions (up to an average of 370 pg/ml), the GFR is less decreased than the RBF. This phenomenon also can be observed at lower plasma A II concentrations (average 200 pg/ml), when the renin-angiotensin system had been previously moderately activated.     

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.     

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.     

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.     

Contribution of angiotensin to the control of medullary hemodynamics

The unique architecture and organization of medullary vasculature permit regional regulation of medullary hemodynamics by vasoactive hormones and are conducive to the operation of the countercurrent multiplication system. Recent studies suggest that an increase in inner medullary blood flow causes medullary solute washout, which in turn decreases passive sodium transport in the thin ascending limb of Henle's loop. In canine models of chronic sodium retention accompanied by activation of the renin-angiotensin system, glomerular filtration rate (GFR), renal blood flow (RBF), and intracortical blood flow distribution were similar to those in normal dogs; however, papillary plasma flow (PPF) was markedly reduced and papillary tissue solute content was increased significantly both during hydropenia and after saline loading. During euvolemic diuresis with loop diuretics, there was an increased renin release associated with a marked reduction in PPF, despite an increase in total RBF. Direct intrarenal infusion of angiotensin II (AngII) (at a dose not affecting GFR and RBF) induced ipsilateral sodium retention, conservation of urinary concentration, and papillary ischemia. These studies provide evidence for regional regulation of medullary hemodynamics by AngII, possibly contributing to sodium retention in chronic salt-retaining states.     

Autoregulation of blood flow in renal medulla of the rat: no role for angiotensin II

Autoregulation of blood flow was assessed by a dual-slit technique in descending and ascending vasa recta of the exposed renal papillae of antidiuretic rats. There was complete autoregulation of blood flow in descending vasa recta. The lower limit of autoregulation was approximately 85 mmHg (1 mmHg = 133.3 Pa) and the upper limit was greater then 160 mmHg. Autoregulation in ascending vasa recta was also good. To test the role of angiotensin II in this autoregulation, the converting enzyme inhibitor captopril was infused. Captopril had no effect on autoregulation of blood flow in either descending or ascending vasa recta. We conclude that blood flow in vasa recta of renal medulla is efficiently autoregulated and that this autoregulation is independent of angiotensin II.     

AT1 receptors in the paraventricular nucleus mediate the hyperthermia-induced reflex reduction of renal blood flow in rats

Increasing body core temperature reflexly decreases renal blood flow (RBF), and the hypothalamic paraventricular nucleus (PVN) plays an essential role in this response. ANG II in the brain is involved in the cardiovascular responses to hyperthermia, and ANG II receptors are highly concentrated in the PVN. The present study investigated whether ANG II in the PVN contributes to the cardiovascular responses elicited by hyperthermia. Rats anesthetized with urethane (1-1.4 g/kg iv) were microinjected bilaterally into the PVN (100 nl/side) with saline (n = 5) or losartan (1 nmol/100 nl) (n = 7), an AT1 receptor antagonist. Body core temperature was then elevated from 37°C to 41°C and blood pressure (BP), heart rate (HR), RBF, and renal vascular conductance (RVC) were monitored. In separate groups losartan (n = 4) or saline (n = 4) was microinjected into the PVN, but body core temperature was not elevated. Increasing body core temperature in control rats elicited significant decreases in RBF (-48 ± 5% from a resting level of 14.3 ± 1.4 ml/min) and MVC (-40 ± 4% from a resting level of 0.128 ± 0.013 ml/min·mmHg), and these effects were entirely prevented by pretreatment with losartan. In rats in which body core temperature was not altered, losartan microinjected into the PVN had no significant effects on these variables. The results suggest that endogenous ANG II acts on AT1 receptors in the PVN to mediate the reduction in RBF induced by hyperthermia.     

Effect of age on cardiovascular responses to static muscular contraction in beagles.

Induced muscular contraction in anesthetized animals results in significant hemodynamic and regional blood flow (RBF) changes. Although reflex cardiovascular responses initiated in contracting muscle have been firmly established, little is known about the effects of age on these responses. Because other reflex responses that involve sympathetic activation appear to be attenuated with age, it was hypothesized that reflex efferent cardiovascular responses that normally occur during muscular contraction would be impaired in senescent dogs. Therefore, hemodynamic and RBF responses to induced static hindlimb contraction (HLC) were evaluated in 8- to 14- and 2- to 3-yr-old beagles during alpha-chloralose anesthesia. Most baseline hemodynamic parameters were similar in both groups, but heart rate was significantly (P < 0.05) higher in old dogs. During HLC, heart rate and blood pressure increased in the young and old dogs. However, increases in stroke volume and cardiac output were greater in old dogs, combined with a reduction in systemic vascular resistance not observed in young dogs. No age-related difference in baseline RBF (microspheres) was observed in six of eight abdominal regional circulations and in each of four skeletal muscle groups. During HLC, RBF reductions occurred in six of eight abdominal organs in young and old dogs. However, the reduction in RBF and concomitant increase in vascular resistance in all eight abdominal regions combined was almost twice as great in young vs. old dogs. In noncontracting skeletal muscle, RBF decreased and vascular resistance increased four times more in young vs. old dogs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal effects of low-dose aminophylline and enprofylline in newborn rabbits

Renal function was studied in 15 newborn New Zealand rabbits administered either 0.6 mg/kg enprofylline intravenously. Each animal acted as its own control. Glomerular filtration rate (GFR) and renal blood flow (RBF) were assessed by the clearances of inulin and para-aminohippuric acid, respectively. Enprofylline, a xanthine with low adenosine antagonistic properties, did not modify urine flow rate, GFR, RBF, renal vascular resistance, filtration fraction, sodium and potassium urinary excretion, whereas administration of theophylline, a potent adenosine antagonist, was associated with a significant increase in diuresis, renal vascular resistance and filtration fraction. The differences observed in the renal effects of theophylline and enprofylline strongly support the view that 1) the renal actions of micromolar concentrations of theophylline are mediated by an antagonism with endogenous renal adenosine; 2) renal adenosine could play a physiological role in the regulation of renal hemodynamics.     

Roles of adrenomedullin 2 in regulating the cardiovascular and sympathetic nervous systems in conscious rats

Recently, a new member of the calcitonin gene-related peptide (CGRP) family, adrenomedullin 2 (AM2) or intermedin (IMD), was identified. AM2/IMD has been shown to have a vasodilator effect in mice and rats and an effect on urine formation in rats. In the present study, we investigated the effects of intravenously infused rat AM2 (rAM2) on blood pressure (BP), heart rate (HR), renal sympathetic nerve activity (RSNA), and renal blood flow (RBF) in conscious unrestrained rats relative to the effects of rat adrenomedullin (rAM) and proadrenomedullin NH2-terminal 20 peptide (rPAMP). Intravenous infusion of rAM2 (5 nmol/kg) significantly decreased BP and increased HR, RSNA, and RBF. These hypotensive and sympathoexcitatory effects diminished after 20 min, and HR returned to control levels 30 min after cessation of the infusion. In contrast, a significant increase in RBF was still evident 60 min after cessation of the peptide infusion. The duration of BP, HR, and RSNA responses was longer with rAM (5 nmol/kg) than with rAM2 infusion, whereas the increases in RBF induced by rAM2 and rAM were similar in their amplitude and duration. Infusion of rPAMP (200 nmol/kg) increased HR and RSNA but had no effect on RBF. Baroreceptor denervation suppressed, but did not diminish, the increases in HR and RSNA to rAM2. These findings indicate that the physiological roles of rAM2 and rAM are similar and that rAM2 also has a long-lasting vasodilator action on the renal vascular bed.