Pressor and vascular responsiveness in renal prehypertensive rabbits with a nonfiltering kidney

This study examined the possibility that the renal tubules are the site of the sensors that respond to renal artery stenosis (RAS) and which initiate the events leading to pressor hyperresponsiveness. A nonfiltering kidney (NFK) was produced in 32 rabbits by 2 hr of total renal ischemia plus permanent ligation of the ureter; the opposite kidney remained undisturbed. Sixteen of these rabbits also received RAS of the NFK. An additional 16 rabbits received RAS without production of a NFK, and 16 more rabbits were sham-operated controls. In acute experiments 3 days later in conscious rabbits, infusions of norepinephrine at several doses resulted in greater increases in mean arterial pressure in the RAS rabbits, with filtering kidneys (2-K, 1-clip) and with NFKs (2-K, 1-clip with NFK), than in the NFK rabbits without RAS (2-K control with NFK) or in the control rabbits (2-K control). Measurements of cardiac output revealed greater increases in total peripheral resistance as well as in mean arterial pressure in response to norepinephrine in the RAS rabbits both without and with a NFK. Because production of a NFK in rabbits did not prevent the development of pressor and vascular hyperresponsiveness 3 days after RAS, these studies indicated that the renal sensors that detect changes in the kidney following RAS and which initiate the series of events leading to pressor and vascular hyperresponsiveness, probably are not located in the renal tubules.     

Vagal afferent activity and renal nerve release of dopamine

To investigate the involvement of vagal afferents in renal nerve release of catecholamines, we compared norepinephrine, dopamine, and epinephrine excretion from innervated and chronically denervated kidneys in the same rat. The difference between innervated and denervated kidney excretion rates was taken as a measure of neurotransmitter release from renal nerves. During saline expansion, norepinephrine excretion from the innervated kidney was not statistically greater than from denervated kidneys. Vagotomy increased norepinephrine release from renal nerves. Thus vagal afferents participated in the suppression of renal sympathetic nerve activity during saline expansion. No significant vagal control of dopamine release by renal nerves was detected under these conditions. Bilateral carotid ligation stimulated renal nerve release of both norepinephrine and dopamine in saline-expanded rats. The effects of carotid ligation and vagotomy were not additive with respect to norepinephrine release by renal nerves. However, the baroreflex-stimulated renal nerve release of dopamine was abolished by vagotomy. Electrical stimulation of the left cervical vagus with a square wave electrical pulse (0.5 ms duration, 10 V, 2 Hz) increased dopamine excretion exclusively from the innervated kidney of hydropenic rats. No significant change in norepinephrine excretion was observed during vagal stimulation. Increased dopamine excretion during vagal stimulation was associated with a larger natriuretic response from the innervated kidney than from its denervated mate (p less than 0.05). We conclude that under appropriate conditions vagal afferents stimulate renal release of dopamine and produce a neurogenically mediated natriuresis.     

Role of baroreflex in the pressor response of rats with hypertension developed by renal artery stenosis

We examined the interrelationships between the pressor response to the administration of norepinephrine and arginine vasopressin and baroreflex function in rats with hypertension of two days' duration induced by heminephrectomy and a clip placed on the right renal artery (2-day clipped rats). Mean arterial pressure was higher in the 2-day clipped rats than in heminephrectomized rats without clips (sham-operated rats). The pressor response in the 2-day clipped rats to both agents increased as compared to the sham-operated rats. This hyperresponsiveness was attenuated by administering an angiotensin II antagonist, [1-Sar, 8-Ile] angiotensin II. Baroreflex sensitivity was studied by measuring changes in arterial pressure and pulse interval in response to the injection of phenylephrine. Baroreflex sensitivity was not decreased but markedly increased in the 2-day clipped rats and unaffected by infusing the angiotensin II antagonist. These results provide evidence that 1) in the 2-day clipped rats there are exaggerated pressor responses to vasoconstrictors; 2) the hyperresponsiveness is not causally related to the change of baroreflex sensitivity; and 3) angiotensin II plays a significant role in the increased pressor responses; however, the baroreflex mechanism is not involved in attenuation of the hyperresponsiveness by the angiotensin II antagonist.     

Prostaglandins in enhanced pressor response in renal prehypertensive rabbits

The role of prostaglandins (PGs) in the pressor response to norepinephrine (NE) was examined in one-kidney, one clip rabbits with renal artery stenosis for 3-day's duration (3-day clipped rabbits) and in sham operated rabbits with one-kidney without renal artery stenosis. An exaggerated pressor response to NE, 800 ng/kg/min, was observed in the 3-day clipped rabbits, and it was abolished by angiotensin II antagonist, [Sar1, Ile8] angiotensin II (AIIA). Treatment with indomethacin, 10 mg/kg, induced hyperresponsiveness to NE in the sham operated rabbits and also produced a further increase in the response in the 3-day clipped rabbits: the enhanced responses with similar levels were not attenuated by AIIA in both groups. A subdepressor dose of PGE2, 800 ng/kg/min, abolished the hyperresponsiveness in the 3-day clipped rabbits, while subdepressor or depressor dose of PGI2, 10 or 20 ng/kg/min did not, but the concurrent infusion of AIIA with PGI2 attenuated it. These results indicate that PGs, in particular PGE2 might be involved in the enhanced pressor response to NE in the 3-day clipped rabbits in addition to the altered renin-angiotensin system.     

Reinvestigation of denervation diuresis and natriuresis in conscious dogs.

The function of innervated and denervated kidney was compared in clearance studies with conscious dogs. The animals were prepared for experiments by unilateral renal denervation and surgical division of the bladder to form two hemibladders enabling separate urine collection from two kidneys. The mean urine flow was 6% higher for the denervated kidney (not significant) while mean differences for osmolar clearance (+ 13%), sodium excretion (+21%) and GFT (+5%) were all significant (P less than 0.05). When corrected to 100 ml GFR, sodium excretion was not significantly higher for the denervated kidney. In most experiments higher sodium excretion on the denefvated side was associated with higher GFR. Thus, contrary to some earlier views, a slight increase in the excretory function which follows denervation of the kidney is demonstrable also in conscious undisturbed animals. The data suggest that increased haemodynamics of the denervated kidney are responsible for higher excretion, but do not exclude a contribution of inhibited tubular reabsorption.     

Effect of acute and chronic renal denervation on renal function after release of unilateral ureteral obstruction in the rat.

The role of the renal nerves in determining renal function after relief of 24-h unilateral ureteral obstruction (UUO) was studied using clearance techniques in anaesthetized rats. Acute renal denervation during the first 1--2 h after relief of UUO resulted in a significant increase in glomerular filtration rate (GFR), renal plasma flow (RPF), urine flow, and sodium and potassium excretion, changes which were not seen in the sham-denervated postobstructive kidney. Acute denervation of sham-operated normal kidneys caused a similar natriuresis and diuresis but with no change in GFR or RPF. Chronic renal denervation 4--5 days before UUO denervated postobstructive controls, while chronic denervation alone was associated with a significantly higher urine flow and sodium excretion rate from the denervated kidney. The effectiveness of renal denervation was confirmed by demonstrating marked depletion of tissue catecholamines in the denervated kidney. It was concluded that renal nerve activity plays a significant but not a major role in the functional changes present after relief of UUO. Chronic renal denervation did not protect against the functional effects of unilateral ureteral obstruction.     

Effect of ventilation on sodium excretion in the anesthetized dog with unilateral renal denervation

We studied if the effect of mechanical ventilation induced to keep arterial blood gas values within normal physiological limits has any influence on renal sodium excretion in anesthetized dogs (n = 17) subjected to acute unilateral renal denervation. Compared to the control and the postcontrol periods, ventilation elevated arterial pO2 from 86 +/- 5 to 96 +/- 5 mmHg and blood pH from 7.37 +/- 0.02 to 7.41 +/- 0.01 while arterial pCO2 was decreased from 38 +/- 2 to 33 +/- 1 mmHg (p less than 0.05 in all cases). Compared to the innervated kidney urine flow, urinary sodium and potassium excretion from the denervated kidney were markedly elevated both during spontaneous respiration and during mechanical ventilation but GFR and cPAH were similar on the two sides. Ventilation decreased sodium excretion by the denervated kidney from 314 +/- 26 to 252 +/- 31 mumols/min/100 g k. w. (p less than 0.05). No other excretory changes were noted either in the innervated or in the denervated kidneys. Difference in sodium excretion between innervated and denervated kidneys was decreased from 209 +/- 19 to 126 +/- 20 mumole/min/100 g k. w. (p less than 0.001), due to the ventilation induced diminution of sodium excretion from the denervated kidney. It is concluded that mechanical ventilation of anesthetized dogs modifies sodium excretion, and this phenomenon can be demonstrated only in the denervated kidney.     

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.     

Effects of renal denervation on the renal responses of anesthetized rats to cyclohexyladenosine

In the present experiments, we tested the hypothesis that renal denervation would attenuate or abolish some of the renal effects of cyclohexyladenosine, a nonmetabolized adenosine receptor agonist. A paired design (left kidney sham-denervated or denervated versus the innervated right kidney) was used in anesthetized rats. Intravenous cyclohexyladenosine (2.3 nmol/min) reduced para-aminohippurate and inulin clearances in both denervated and sham-denervated kidneys; these effects were increased rather than decreased in denervated kidneys. Similarly, cyclohexyladenosine decreased the excretion of Na+ and K+ more in denervated than in innervated kidneys. Renal plasma flow was decreased by cyclohexyladenosine, without a corresponding increase in the arteriorenal venous difference in plasma renin concentrations, and arterial plasma renin concentration decreased in all rats given cyclohexyladenosine, suggesting inhibition of renin secretion. No differences in the latter variables were noted in denervated versus sham-denervated kidneys. Since cyclohexyladenosine produced effects in denervated kidneys which were equal to or greater than the effects in sham-denervated kidneys, it is concluded that these effects are mediated by direct actions, rather than by inhibition of transmitter release from the renal nerves.     

Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 micrograms/min, i.v.), an alpha 1-adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (-67 +/- 9 vs. -33 +/- 8%), glomerular filtration rate (-60 +/- 9 vs. -7 +/- 20%), urine flow (-61 +/- 7 vs. -24 +/- 11%), sodium excretion (-51 +/- 15 vs. -32 +/- 21%), and fractional excretion of sodium (-50 +/- 9 vs. -25 +/- 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (-54 +/- 10 vs. -30 +/- 14%), glomerular filtration rate (-51 +/- 11 vs. -19 +/- 17%), urine flow (-55 +/- 10 vs. -39 +/- 10%), sodium excretion (-70 +/- 9 vs. -59 +/- 11%), and fractional excretion of sodium (-53 +/- 10 vs. -41 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Excretory function of denervated kidney after inhibition of prostaglandin synthesis and furosemide administration in conscious dogs

The experiments were carried out on unanaesthetized dogs with exteriorized ureters for separate urine collection from the left (denervated) and the right (intact) kidney. The osmolality and concentrations of sodium, potassium, calcium, magnesium, zinc, copper, chloride and creatinine were determined in the plasma as well as in the urine of the two kidneys. The function of the denervated and the innervated kidney was compared prior to and after indomethacin administration (5.0 mg/kg b.w.). The excretory function of both kidneys was also compared after furosemide treatment alone (0.5 mg/kg b.w.) as well as indomethacin pretreatment. Renal denervation increased urine flow rate, calcium and copper excretion. After administration, sodium excretion from the denervated kidney was higher than that from the intact one. Calcium excretion of the two kidneys did not differ significantly, while copper excretion from the denervated kidney was diminished, Furosemide administration after pretreatment with indomethacin did not lead to any difference between the denervated and intact kidney. The results show that renal nerves and prostaglandins participate jointly in the regulation of sodium, copper and calcium excretion. Renal prostaglandins do not change the response of the denervated kidney to furosemide as compared to the intact kidney.     

Interaction among atrial natriuretic factor (ANF), vasopressin, and renal nerves in terms of renal responses in rats.

The relationship between the renal nerves and vasopressin in terms of the natriuretic and diuretic responses to atrial natriuretic factor (ANF--0.25 microgram/kg/min for 15 min), was investigated in unilaterally denervated anesthetized rats before and after the administration of a vasopressin V2 specific antagonist (AVPX)--(40 micrograms/kg bolus followed by 0.4 microgram/kg/min infusion). Administration of the AVPX or ANF did not alter the arterial pressure. Acute renal denervation or AVPX administration independently produced significant increases in sodium and water excretion. ANF infusion by itself produced a greater increase in urine flow and sodium excretion from the denervated kidney compared to the intact kidney before the administration of AVPX. However, after the administration of AVPX renal responses to ANF from the intact kidneys were enhanced such that they were not significantly different from the denervated kidneys. These results suggest that the full physiological response to ANF may be masked by tonic renal nerve activity or antidiuretic actions of vasopressin. Furthermore, since combined renal denervation and AVPX administration does not produce any greater potentiation of the renal responses to ANF than either of these manipulations alone, it is suggested that they may act via a common mechanism, possibly altering activity in the renal nerves.     

Time course of denervation diuresis and natriuresis in the anaesthetized rat

The effect of unilateral renal sympathectomy on renal excretion of water and sodium was studied in three groups of Inactin-anaesthetized rats: 1-3, 4-19, and 20-35 weeks after denervation. Increased sodium excretion from the denervated kidney in the absence of changes in GFR was observed up to 35 weeks following renal denervation. Thus, in a functional sense, renal reinnervation may have only been partial during the time interval studied.     

Baroreflexes prevent neurally induced sodium retention in angiotensin hypertension

Recent studies indicate that renal sympathetic nerve activity is chronically suppressed during ANG II hypertension. To determine whether cardiopulmonary reflexes and/or arterial baroreflexes mediate this chronic renal sympathoinhibition, experiments were conducted in conscious dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-h urine collection from denervated (Den) and innervated (Inn) kidneys. Dogs were studied 1) intact, 2) after thoracic vagal stripping to eliminate afferents from cardiopulmonary and aortic receptors [cardiopulmonary denervation (CPD)], and 3) after subsequent denervation of the carotid sinuses to achieve CPD plus complete sinoaortic denervation (CPD + SAD). After control measurements, ANG II was infused for 5 days at a rate of 5 ng. kg(-1). min(-1). In the intact state, 24-h control values for mean arterial pressure (MAP) and the ratio for urinary sodium excretion from Den and Inn kidneys (Den/Inn) were 98 +/- 4 mmHg and 1.04 +/- 0.04, respectively. ANG II caused sodium retention and a sustained increase in MAP of 30-35 mmHg. Throughout ANG II infusion, there was a greater rate of sodium excretion from Inn vs. Den kidneys (day 5 Den/Inn sodium = 0.51 +/- 0.05), indicating chronic suppression of renal sympathetic nerve activity. CPD and CPD + SAD had little or no influence on baseline values for either MAP or the Den/Inn sodium, nor did they alter the severity of ANG II hypertension. However, CPD totally abolished the fall in the Den/Inn sodium in response to ANG II. Furthermore, after CPD + SAD, there was a lower, rather than a higher, rate of sodium excretion from Inn vs. Den kidneys during ANG II infusion (day 5 Den/Inn sodium = 2.02 +/- 0.14). These data suggest that cardiac and/or arterial baroreflexes chronically inhibit renal sympathetic nerve activity during ANG II hypertension and that in the absence of these reflexes, ANG II has sustained renal sympathoexcitatory effects.     

脑室内注射高张盐水抑制近曲小管对水和钠的重吸收

实验在麻醉大鼠上进行。用锂清除率为指标观察脑室内注射高张盐水对近曲小管重吸收水和钠的影响。在切断单侧肾神经的动物中,脑室内注射高张盐水后的锂清除率与肾小球滤过率比值在去神经侧肾脏从0.37±0.04增加至0.51±0.05(P<0.01);神经完好侧肾脏则从0.26±0.03增加至0.31±0.04(P<0.05);双侧肾脏的肾小球滤过率、尿量、尿钠和尿钾量均增加,且去肾神经肾脏的增加幅度高于肾神经完好肾脏。在肾小管微穿刺实验中,脑室内注射高张盐水后,近曲小管末段小管液流量从24.42±1.84nl/min增加至31.86±3.09nl/min(P<0.01),小管液的渗透压无显著变化。以上实验结果表明,脑室内注射高张盐水引起的利尿、尿钠增多反应与肾小球滤过率增加和近曲小管对水、钠重吸收减少有关,体液因素在该反应中可能起主要作用。     

Long-term control of renal blood flow: what is the role of the renal nerves?

We have developed a system for long-term continuous monitoring of cardiovascular parameters in rabbits living in their home cage to assess what role renal sympathetic nerve activity (RSNA) has in regulating renal blood flow (RBF) in daily life. Blood pressure, heart rate, locomotor activity, RSNA, and RBF were recorded continuously for 4 wk. Beginning 4-5 days after surgery a circadian rhythm, dependent on feeding time, was observed. When averaged over all days RBF to the innervated and denervated kidneys was not significantly different. However, control of RBF around these mean levels was dependent on the presence of the renal sympathetic nerves. In particular we observed episodic elevations in heart rate and other parameters associated with activity. In the denervated kidney, during these episodic elevations, the increase in renal resistance was closely related to the increase in arterial pressure. In the innervated kidney the renal resistance response was significantly more variable, indicating an interaction of the sympathetic nervous system. These results indicate that whereas overall levels of RSNA do not set the mean level of RBF the renal vasculature is sensitive to episodic increases in sympathetic nerve activity.     

Dopamine production by the isolated perfused rat kidney

We used isolated perfused rat kidneys to examine dopamine (DA) production and its relation to renal function. Both innervated and chronically surgically denervated kidneys perfused with a solution containing neither albumin nor tyrosine, excreted 0.2 +/- 0.1 ng DA X min-1 X g wet weight-1 during the 10-min collection period between 30 and 40 min after starting perfusion. When perfused with 6.7% albumin, without tyrosine, innervated kidneys excreted 1.0 +/- 0.06 ng DA X min-1 X g-1 and denervated kidneys excreted 1.0 +/- 0.07 DA X min-1 X g-1. When 0.03 mM tyrosine was included in the albumin perfusate, innervated kidneys excreted 1.2 +/- 0.1 ng DA X min-1 X g-1 (p less than 0.1). Under these conditions DA excretion continued for at least 100 min at which time it was 0.6 ng X min-1 X g-1 and 86 ng/g kidney weight had been excreted. Denervated kidneys perfused with albumin + tyrosine excreted 0.9 +/- 0.13 ng DA X min-1 X g-1. Renal stores of free DA, conjugated DA, and dihydroxyphenylalanine (DOPA) could have provided at the most 30 ng/g of DA. Carbidopa inhibited DA excretion completely. DA excretion did not correlate with renal vascular resistance, inulin clearance, or fractional sodium excretion. In summary, nonneural tissue in isolated perfused kidneys produced DA at the same rate as denervated kidneys in vivo. Less than one-third of the DA produced by isolated kidneys could have come from intrarenal stores of DOPA, free DA, and conjugated DA; the rest was synthesized from unknown precursors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal denervation modulates angiotensin receptor expression in the renal cortex of rabbits with chronic heart failure

Excessive sympathetic drive is a hallmark of chronic heart failure (HF). Disease progression can be correlated with plasma norepinephrine concentration. Renal function is also correlated with disease progression and prognosis. Because both the renal nerves and renin-angiotensin II system are activated in chronic HF we hypothesized that excessive renal sympathetic nerve activity decreases renal blood flow in HF and is associated with changes in angiotensin II type 1 receptor (AT1R) and angiotensin II type 2 receptor (AT2R) expression. The present study was carried out in conscious, chronically instrumented rabbits with pacing-induced HF. We found that rabbits with HF showed a decrease in mean renal blood flow (19.8±1.6 in HF vs. 32.0±2.5 ml/min from prepace levels; P<0.05) and an increase in renal vascular resistance (3.26±0.29 in HF vs. 2.21±0.13 mmHg·ml(-1)·min in prepace normal rabbits; P<0.05) while the blood flow and resistance was not changed in HF rabbits with the surgical renal denervation. Renal AT1R expression was increased by ～67% and AT2R expression was decreased by ～87% in rabbits with HF; however, kidneys from denervated rabbits with HF showed a near normalization in the expression of these receptors. These results suggest renal sympathetic nerve activity elicits a detrimental effect on renal blood flow and may be associated with alterations in the expression of angiotensin II receptors.