Renal Nerve Activity Responses Research Articles

Bradykinin and protein kinase C activation fail to stimulate renal sensory neurons in hypertensive rats.

In normotensive rats, renal sensory receptor activation by increased ureteral pressure results in increased ipsilateral afferent renal nerve activity, decreased contralateral efferent renal nerve activity, and contralateral diuresis and natriuresis, a contralateral inhibitory renorenal reflex response. In spontaneously hypertensive rats (SHR), increasing ureteral pressure fails to increase afferent renal nerve activity. The nature of the inhibitory renorenal reflexes indicates that an impairment of the renorenal reflexes would contribute to the increased efferent renal nerve activity in SHR. We therefore examined whether there was a general decrease in the responsiveness of renal sensory receptors in SHR by comparing the afferent renal nerve activity responses to bradykinin in SHR and Wistar-Kyoto rats (WKY). In WKY, renal pelvic perfusion with bradykinin at 4, 19, 95, and 475 micromol/L increased afferent renal nerve activity by 1066 +/- 704, 2127 +/- 1121, 3517 +/- 1225, and 4476 +/- 1631% x second (area under the curve of afferent renal nerve activity versus time). In SHR, bradykinin at 4 to 95 micromol/L failed to increase afferent renal nerve activity. Bradykinin at 475 micromol/L increased afferent renal nerve activity in only 6 of 10 SHR. In WKY, renal pelvic perfusion with the phorbol ester 4beta-phorbol 12,13-dibutyrate, known to activate protein kinase C, resulted in a peak afferent renal nerve activity response of 24 +/- 4%. However, 4beta-phorbol 12,13-dibutyrate failed to increase afferent renal nerve activity in SHR. These findings demonstrate decreased responsiveness of renal pelvic sensory receptors to bradykinin in SHR. The impaired afferent renal nerve activity responses to bradykinin in SHR may be due to a lack of protein kinase C activation or a defect in the intracellular signaling mechanisms distal to protein kinase C activation.

Response of renal nerve activity to high NaCl food intake in dogs with chronic bile duct ligation

Hepatic sensory systems are thought to play an important role in the response of renal nerve activity and natriuresis to oral NaCl load. In this study, responses of renal nerve activity and urinary Na+ and Cl- excretions to a high-NaCl food intake (20 g/kg boiled rice containing 0.4 g/kg NaCl) were examined in sham-operated dogs (n = 12) and dogs with chronic bile duct ligation (CBDL; n = 10). In sham-operated dogs, renal nerve activity gradually decreased and reached minimal value (50% +/- 7% of the control value) at 100 minutes after the high-NaCl food intake and remained depressed until 4 hours after the food intake. Of the orally administered sodium and chloride, 27% +/- 5% and 23% +/- 6% were excreted over the following 4 hours, respectively. In CBDL dogs, the decrease in renal nerve activity induced by the high-NaCl food was completely abolished and only 4% +/- 1% of the loaded Na+ and 3% +/- 2% of the loaded Cl- were excreted. Furthermore, liver tissue norepinephrine concentration in CBDL dogs decreased to 21% of that of sham-operated dogs. These results suggest that (1) In CBDL dogs, the decrease in renal nerve activity induced by a high-NaCl food is completely abolished, probably because of the impairment of hepatic neural regulation. (2) The lack of renal nerve response may contribute, at least in part, to the abnormalities in body fluid homeostasis in cirrhosis. (Hepatology 1996 Feb;23(2):303-9)

Intravenously-injected naloxone reverses the decrease in renal sympathetic nerve activity seen during hypotensive hemorrhage in conscious rabbits by acting through central mechanisms

The response of renal sympathetic nerve activity (RNA) to hemorrhage was examined in chronically-instrumented conscious rabbits. Hemorrhage was induced at a rate of 5 ml/kg per min until the mean arterial pressure fell below 40 mmHg. The mean arterial pressure then remained at around 80 mmHg until 10 ml/kg of hemorrhage (normotensive hemorrhage) before falling to below the pre-hemorrhagic control level (hypotensive hemorrhage). The RNA response showed a biphasic pattern, i.e., it increased during normotensive hemorrhage, then fell below the control level during hypotensive hemorrhage. To examine the mechanism involved in this decrease in RNA, naloxone (7.5 μmol/kg), an opioidergic receptor antagonist, was intravenously injected 1 min after the end of hemorrhage. Intravenous injection of naloxone caused an increase in mean arterial pressure and RNA to the level seen during normotensive hemorrhage. These results indicate that the decrease in RNA induced by hypotensive hemorrhage is mediated by opioidergic receptors. To determine whether the effects of naloxone are mediated via central or peripheral opioidergic receptors, naloxone was replaced by an equimolar solution of methylnaloxone, a form unable to cross the blood-brain barrier. Neither the mean arterial pressure nor RNA was significantly altered by administration of methyl naloxone. These results suggest that the effects of naloxone on both the RNA and the mean arterial pressure are mediated via central opioidergic receptors, i.e., the sympathoinhibition induced by hypotensive hemorrhage is mediated via the stimulation of central opioidergic receptors.

P-1075 - Role of nitric oxide in the response of renal sympathetic nerve activity to hemorrhage in conscious rats

P-1075 - Role of nitric oxide in the response of renal sympathetic nerve activity to hemorrhage in conscious rats

Brain ‘Ouabain’ Mediates Sympathetic Hyperactivity in Congestive Heart Failure

In congestive heart failure (CHF), endogenous compounds with ouabainlike activity (OLA) may contribute to the maintenance of the circulatory homeostasis by peripheral as well as central effects. In the present study, we assessed changes in peripheral (plasma and left ventricle) and central (pituitary, hypothalamus, pons, and cortex) OLA in two animal models of CHF and determined whether brain OLA mediates sympathetic hyperactivity in CHF. Cardiomyopathic hamsters with their controls were studied at 9 months of age for tissue OLA. Rats were studied 4 weeks after acute coronary artery ligation for tissue OLA and sympathetic activity. In both models, left ventricular end-diastolic pressure was markedly increased. CHF was associated with significant increases in both plasma and tissue OLA in both models. In the brain, the most marked (twofold to threefold) increases occurred in the hypothalamus. In vitro, all OLA measured could be blocked by antibody Fab fragments (Digibind). Conscious rats with CHF showed elevated plasma catecholamines and enhanced responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to air stress and to intracerebroventricular (ICV) injection of the alpha 2-adrenergic receptor agonist guanabenz compared with sham-operated rats. ICV administration of the Fab fragments did not change resting RSNA or responses to air stress at 1 hour. However, 18 hours after injection of the Fab fragments, resting RSNA levels had significantly decreased compared with the control values, and plasma catecholamine levels had decreased to control values.(ABSTRACT TRUNCATED AT 250 WORDS)

Different Responses of Renal Blood Flow and Sympathetic Nerve Activity to Captopril and Nicardipine in ConsciousRenal Hypertensive Rabbits

To elucidate the roles of endogenous angiotensin II (AII) and renal sympathetic nerve activity (RSNA) in modulation of renal blood flow (RBF), we recorded RBF and RSNA in conscious two-kidney, one-clip (2K1C) hypertensive rabbits with blood pressure (BP) reduced to a similar extent by captopril (5 mg/kg) and nicardipine (4.3 micrograms/kg/min). We measured plasma concentrations of AII, arginine vasopressin (AVP), and norepinephrine (NE). Despite comparable depressor effects, changes in RBF showed different profiles with the two drugs in renal hypertensive rabbits. After captopril injection, RBF was consistently increased to 143 +/- 7%. In contrast, with nicardipine infusion, RBF was initially increased to 114 +/- 5% and then significantly decreased to 86 +/- 4%. The increase in RSNA was greater with captopril than with nicardipine. Plasma concentration of AII was decreased with captopril but significantly increased with nicardipine. In sham-clipped normotensive rabbits in which plasma AII was not increased, RBF was not reduced with nicardipine. Thus, vasoconstrictor actions of RSNA and increased AII may have overcome the vasodilatory effect of nicardipine in conscious renal hypertensive rabbits. Because the increase in RSNA was smaller with nicardipine, we speculate that the vasoconstriction induced by AII, as well as background BP level, played a substantial role in determining RBF.

Essential fatty acid deficiency impairs the responsiveness of renal pelvic sensory receptors

The role of prostaglandins in renal sensory receptor activation was examined in rats fed an essential fatty acid-deficient (EFAD) diet to cause tissue arachidonate depletion. Littermates fed a standard diet were used as controls. In anesthetized rats, the increases in afferent renal nerve activity due to increasing ureteral pressure 2.5, 5, 7.5, 10, 12.5, and 15 mmHg were significantly reduced by the EFAD diet (P < 0.02): 3 +/- 5, 3 +/- 5, 11 +/- 5, 9 +/- 5, 19 +/- 3, and 17 +/- 5%, respectively, in EFAD rats and 23 +/- 11, 36 +/- 15, 50 +/- 15, 52 +/- 8, 72 +/- 17, and 90 +/- 19%, respectively, in control rats. In EFAD rats, addition of prostaglandin E2 (PGE2) to the renal pelvic perfusate restored the afferent renal nerve activity response to increased ureteral pressure toward that in control rats. PGE2 had no effect in control rats. Also the afferent renal nerve activity responses to renal pelvic perfusion with bradykinin at 4, 20, 100, and 500 micrograms/ml were significantly suppressed by the EFAD diet (P < 0.01): 13 +/- 15, 5 +/- 7, 60 +/- 19, and 63 +/- 20%, respectively, in EFAD rats and 122 +/- 23, 142 +/- 31, 172 +/- 19, and 190 +/- 39%, respectively, in control rats. These results demonstrate an important role for arachidonate metabolites, particularly PGE2, in renal sensory receptor activation. Together with our previous studies showing that indomethacin blocks the afferent renal nerve activity responses to increased ureteral pressure or bradykinin, the present studies provide strong evidence for an essential role of prostaglandins in renal sensory receptor activation.

Mediation of baroreceptor inhibition of sympathetic nerve activity via both a brainstem and spinal site in rats.

1. The possible involvement of a spinal site of sympatho-inhibitory action in the baroreceptor reflex pathways was investigated by determining the effect of phenylephrine-induced, baroreceptor-mediated inhibition on a spinally evoked excitatory response of renal nerve activity before, during and after removal of tonic descending excitatory drive from the rostral ventrolateral medulla (RVLM). 2. Stimulation of descending excitatory axons at the C4 vertebral level evoked a highly reproducible excitatory response (mean variance, 2.2 +/- 0.6%) in a renal sympathetic nerve with a latency of 72 +/- 5.7 ms and duration of 211 +/- 32 ms. 3. Following baroreceptor activation, the magnitude of this spinally evoked response was reduced by 33.5 +/- 4.2% compared with control spinal response. 4. To remove tonic descending excitatory drive, glycine was microinjected bilaterally into the RVLM (RVLM block); this briefly and reversibly abolished spontaneous sympathetic nerve activity. 5. Following RVLM block, the spinally evoked response in a renal sympathetic nerve was inhibited by 16.9 +/- 4.4% during baroreceptor activation. 6. Intrathecal administration of the glycine antagonist strychnine to the lower thoracic segments of the spinal cord virtually abolished this inhibition. 7. It was concluded that baroreceptor inhibition of sympathetic activity occurs at a spinal site as well as a supraspinal one. Glycine is a likely mediator of the inhibition at the spinal site.

Responses of renal nerve activity and urinary NaCl excretion to high NaCl diet in dogs with liver cirrhosis

Here we studied the mechanism of thrombolytic response (THR) induced by angiotensin converting enzyme (ACE-I) in vivo in anaesthetised Wistar rats with extracorporeal circulation. Intravenous injections of ACE-Is, i.e. perindopril or quinapril at non-hypotensive doses of 3–30 μg kg−1 produced a dose-dependent thrombolysis that was associated with a parallel rise in arterial blood levels of 6-keto-PGF1α, but not those of TXB2 or PGE2. L-NAME at a dose of 5 mg kg−1 affected significantly neither ACE-I-induced thrombolysis nor prostacyclinemia; however, the pre-treatment with icatibant (0.1–0.5 mg kg−1) abolished both effects. The selective COX-1 inhibitor, SC 560 (100–300 μg kg−1 i.v.), or a would be selective COX-3 inhibitor—paracetamol (acetaminophen, 1–3 mg kg−1), both agents induced a transient thrombolysis and slightly potentiated thrombolysis by ACE-Is. In contrast, selective COX-2 inhibitors (rofecoxib⪢celecoxib>nimesulide>NS 398) were thrombogenic, and abolished THR and rise in 6-keto-PGF1α induced by ACE-Is.Summing up, in our in vivo bioassay system ACE-Is such as quinapril, perindopril or captopril at non-hypotensive doses evoke THR that is mediated by endogenous bradykinin and prostacyclin derived from endothelial COX-2.

Renal sensory receptor activation by calcitonin gene-related peptide.

In anesthetized rats we examined whether calcitonin gene-related peptide activated renal pelvic sensory receptors and, if so, whether activation of renal pelvic calcitonin gene-related peptide receptors contributes to the inhibitory renorenal reflex response to renal mechanoreceptor stimulation. Calcitonin gene-related peptide (0.0026, 0.026, 0.26, and 2.6 mumol/L) administered into the renal pelvis increased ipsilateral afferent renal nerve activity in a concentration-dependent fashion (32 +/- 14%, 69 +/- 19%, 93 +/- 26%, and 253 +/- 48% [all P < .01], respectively). The increases in ipsilateral afferent renal nerve activity elicited by calcitonin gene-related peptide were associated with increases in contralateral urinary sodium excretion. The calcitonin gene-related peptide receptor antagonist human CGRP (h-CGRP) (8-37) (0.01, 0.1, 1.0, and 10 mumol/L) decreased the ipsilateral afferent renal nerve activity response to renal pelvic administration of calcitonin gene-related peptide (0.26 mumol/L) in a concentration-dependent fashion (29 +/- 4%, 33 +/- 12%, 76 +/- 9% [P < .01], and 86 +/- 13% [P < .01], respectively). In the presence of renal pelvic perfusion with vehicle, an increase in ureteral pressure of 5, 10, and 20 mm Hg increased ipsilateral afferent renal nerve activity by 13 +/- 7%, 41 +/- 7% (P < .01), and 95 +/- 15% (P < .01) and contralateral urinary sodium excretion by 8 +/- 1%, 24 +/- 4%, and 42 +/- 7% (all P < .05). The ipsilateral afferent renal nerve activity and contralateral natriuretic responses to graded increases in ureteral pressure (5 to 20 mm Hg) were unaltered by renal pelvic perfusion with h-CGRP (8-37) at 1.0 and 10 mumol/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal vascular and sympathetic nerve responses to hypotension induced by platelet-activating factor in anesthetized dogs

This experiment was designed to determine renal sympathetic and renal vascular responses to platelet-activating factor (PAF)-induced hypotension in anesthetized dogs with and without systemic baroreceptor denervation. The left kidney was perfused at a constant flow, and renal perfusion pressure and efferent left renal sympathetic nerve activity were measured simultaneously. Intrarenal injection of PAF (1.25−5.0×10 −2 μg/kg, n = 6) produced a dose-dependent increase in renal perfusion pressure without any change in systemic blood pressure. An intravenous injection of PAF (10 μg/kg) to intact animals ( n = 7) caused an initial increase in renal nerve activity (157±14%) followed by a gradual reduction below baseline (72±7%) with concomitant systemic hypotension (from 116±7 to 46±6 mmHg). Renal perfusion pressure increased significantly from 84±2 to 161±33 mmHg concomitant with an increase in renal nerve activity at 1 min and was maintained at this elevated level throughout the experiment. Similar responses of renal nerve activity and renal perfusion pressure were found in animals with complete systemic baroreceptor denervation ( n = 7). These renal suggest that renal vascular response during PAF-induced hypotension may presumably be mediated by a direct vasoconstrictor effect of PAF on the renal vasculature and that baroreceptor reflex is not involved in either renal sympathetic or renal vascular changes.

Role of prostaglandins in renal sensory receptor activation by substance P and bradykinin.

In anesthetized rats increasing ureteral pressure results in an increase in ipsilateral afferent renal nerve activity and a reflex increase in contralateral urine flow rate and urinary sodium excretion that is dependent on intact prostaglandin synthesis. Activation of renal pelvic substance P receptors contributes to the renorenal reflex responses to increased ureteral pressure. Because these data suggested that renal sensory receptors could be activated by both prostaglandins and substance P we examined whether activation of renal sensory receptors by substance P was dependent on intact prostaglandin synthesis. The renal pelvis was perfused with capsaicin, 2.5 micrograms/ml, or substance P, 4 micrograms/ml, before and during renal pelvic perfusion with the prostaglandin synthesis inhibitor indomethacin, 50 micrograms/ml. Indomethacin reduced the peak ipsilateral afferent renal nerve activity responses to capsaicin and substance P by 83 +/- 15% and 81 +/- 8%, respectively, as well as the contralateral diuretic and natriuretic responses. We also examined the effects of renal pelvic administration of indomethacin on the responses to renal pelvic perfusion with bradykinin. Bradykinin, 20 micrograms/ml, increased peak ipsilateral afferent renal nerve activity by 197 +/- 47% and contralateral urine flow rate and urinary sodium excretion by 31 +/- 6 and 20 +/- 6%, respectively. Indomethacin reduced the ipsilateral afferent renal nerve activity response by 76 +/- 9% and abolished the contralateral diuretic and natriuretic responses to bradykinin. We conclude that renal sensory receptor activation by capsaicin, substance P, and bradykinin is dependent on intact renal prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Sympathoinhibitory action of rilmenidine in conscious sinoaortically denervated rats.

The responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to rilmenidine administration and changes in these responses after idazoxan or yohimbine pretreatment were investigated in conscious sinoaortically denervated rats. Intravenous (i.v.) injection of rilmenidine (300 and 600 micrograms/kg) dose-dependently reduced MAP (16 and 24%, respectively) and RSNA (31 and 56%, respectively), whereas bradycardia was similar at both doses of the drug. Intracisternal (i.c.) pretreatment with idazoxan (5 micrograms/kg), alpha 2-adrenoceptor antagonist with a high affinity to imidazoline receptors (IR) prevented rilmenidine-induced decreases in MAP but not in RSNA and HR. Rilmenidine (300 micrograms/kg i.c.) significantly decreased MAP by 24%, RSNA by 32%, and HR by 13%. Pretreatment with idazoxan (1 microgram/kg i.c.) significantly attenuated the hypotensive and sympathoinhibitory effects of rilmenidine, whereas i.c. pretreatment with equimolar to 10-fold higher doses of yohimbine, an alpha 2-antagonist that binds poorly with IR, did not. Both idazoxan and yohimbine failed to affect the rilmenidine-induced bradycardia, however. We concluded that (a) rilmenidine exhibits more marked hypotensive effect when injected i.c. than when injected i.v., (b) a part of the inhibitory effect of i.v.-injected rilmenidine on RSNA may be exerted through idazoxan-insensitive mechanisms which might be activated by peripheral action of the drug, and (c) the hypotensive action of rilmenidine relates more to the interaction with IR than with alpha 2-adrenoceptors.

Control of sympathetic nerve activity by vagal mechanoreflexes is blunted in heart failure.

Previous studies have documented abnormalities of arterial baroreflexes in animals and patients with congestive heart failure. This study determined whether cardiopulmonary reflex control of sympathetic nerve activity was abnormal in a canine model of low-output heart failure induced by rapid ventricular pacing. We stimulated mechanoreceptors throughout the cardiopulmonary region by volume expansion and left atrial mechanoreceptors selectively by inflating small balloons at the junctions of the pulmonary veins and left atrium. Responses of renal sympathetic nerve activity and left atrial and systemic arterial pressures were recorded. In the control group, 15% volume expansion raised left atrial pressure 3.5 +/- 0.8 mm Hg and resulted in a 70 +/- 8% reduction in renal nerve activity. In the heart failure group, 15% volume expansion resulted in a 6.8 +/- 3.0 mm Hg rise in left atrial pressure with only a 16 +/- 20% reduction in renal nerve activity (p < 0.01). When volume expansion was performed after pretreatment with hemorrhage to lower left atrial pressure to the normal range in the heart failure group, the markedly attenuated response in the heart failure group persisted. After vagotomy, volume expansion elicited no change in renal nerve activity. Inflation of the atrial balloons caused a 28 +/- 9% reduction in renal sympathetic nerve activity and a 13 +/- 4 mm Hg decrease in arterial pressure in the control group. Renal nerve activity (-5 +/- 3%) and mean arterial pressure (-1 +/- 1 mm Hg) did not change with balloon inflation in the heart failure group. We conclude that dogs with low-output heart failure exhibit marked attenuation of cardiopulmonary mechanoreflex control of sympathetic nerve activity. This attenuated response is mediated via cardiac vagal afferent fibers and is due to either abnormalities in cardiopulmonary baroreceptors or abnormalities in the central nervous system.

Dietary Na, age, and baroreflex control of heart rate and renal sympathetic nerve activity in rats.

Heart rate (HR) and renal sympathetic nerve activity (RSNA) responses to ramp changes in blood pressure (BP) by (de)pressor agents and to acute volume expansion were recorded in conscious young, mature, and old Wistar rats maintained for 4 wk on diets containing low, control, or high dietary Na. Both HR and RSNA responses to BP increases or decreases were attenuated on low-Na diet compared with control Na diet. On high-Na diet, HR responses to BP changes and RSNA responses to BP increases were also attenuated, but in contrast the excitatory response of RSNA to BP decreases was augmented. The inhibitory RSNA response, but not the HR response, to volume expansion was significantly attenuated in young rats on high-Na diet but not on low-Na diet. The effects of both low and high dietary Na on HR and RSNA responses were most marked in young rats, less in mature rats, and even less in old rats. These results indicate a discordance of high dietary Na-induced changes in HR vs. RSNA control by the arterial and cardiopulmonary baroreflex, which is suggestive of central mechanisms affected by dietary Na. The developing nervous system appears to be the most responsive to dietary Na.

Brain ouabain and central effects of dietary sodium in spontaneously hypertensive rats.

High sodium intake (HNa) increases brain ouabainlike activity (OLA) in rats. In spontaneously hypertensive rats (SHR), HNa exaggerates development of hypertension and pressor and sympathoexcitatory responses to stress. To investigate whether dietary sodium-induced changes in brain OLA play a functional role, responses of mean arterial pressure (MAP), heart rate (HR), and renal sympathetic nerve activity (RSNA) to intracerebroventricular ouabain and to mental stress and intracerebroventricular alpha 2-adrenoceptor agonist guanabenz alone or preceded by intracerebroventricular ouabain were recorded in conscious SHR and Wistar-Kyoto (WKY) rats maintained from 4 to 8 weeks of age on different sodium diets: 1) low sodium intake (LNa, 17 mumol), 2) normal sodium intake (NNa, 101 mumol), and 3) HNa (1,370 mumol). SHR on NNa showed significantly higher MAP and RSNA compared with WKY rats on NNa. HNa or LNa significantly increased or decreased MAP but had no effects on resting RSNA in SHR and had no effects on resting MAP and RSNA in WKY rats. Intracerebroventricular ouabain induced dose-dependent increases in MAP, RSNA, and HR. In both SHR and WKY rats, LNa significantly enhanced these responses. In contrast, HNa significantly attenuated these responses only in SHR. Air stress increased and intracerebroventricular guanabenz decreased MAP, HR, and RSNA. The magnitudes of increases and decreases were significantly larger in SHR than in WKY rats. In WKY rats, dietary sodium did not change these responses. In contrast, in SHR, HNa significantly enhanced MAP, HR, and RSNA responses to air stress or intracerebroventricular guanabenz.(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory renorenal reflexes: a role for renal prostaglandins in activation of renal sensory receptors

In anesthetized rats, activation of renal sensory receptors with a mechanical stimulus (increased ureteral pressure) and a chemical stimulus (renal pelvic perfusion with 0.9 M NaCl) results in an increase in ipsilateral afferent renal nerve activity and a reflex increase in contralateral urine flow rate and urinary sodium excretion, i.e., a contralateral inhibitory renorenal reflex. Because both interventions are known to increase renal prostaglandin (PG) synthesis, we examined whether renal PGs were involved in the renorenal reflex response to renal sensory receptor stimulation. In the first part, mechanical and chemical activation of renal sensory receptors was performed in the absence and presence of renal pelvic perfusion with indomethacin or meclofenamate (0.2 micrograms/min). Indomethacin inhibited the ipsilateral afferent renal nerve activity response to increased ureteral pressure (7 +/- 2 vs. 38 +/- 10%, P less than 0.01) and renal pelvic perfusion with 0.9 M NaCl (3 +/- 3 vs. 28 +/- 5%, P less than 0.01) and the contralateral diuretic and natriuretic responses in the absence of any renal hemodynamic changes. Similar effects were produced by meclofenamate. In the second part, mechanical and chemical activation of renal sensory receptors was performed in the presence of renal pelvic perfusion with vehicle, indomethacin, and indomethacin plus PGE2 (20 micrograms/min). Addition of PGE2 to the renal pelvic perfusate in indomethacin-treated kidneys restored the responses to mechanical and chemical activation of renal sensory receptors to levels not different from their pre-indomethacin control values. We conclude that PGs in the renal pelvic area are involved in inhibitory renorenal reflex responses to mechanical and chemical activation of renal sensory receptors.

Neural control of urinary sodium excretion during hypertonic NaCl load in conscious rabbits: role of renal and hepatic nerves and baroreceptors

We examined responses of renal nerve activity, urine flow, and urinary Na+ excretion to a hypertonic NaCl infusion in chronically instrumented conscious rabbits with unilateral renal denervation. The intravenous infusion of 20% NaCl, at 0.2 ml/min for 30 min, increased plasma osmolality by 27 +/- 5 mOsm/kg, and plasma Na+ by 16 +/- 3 mEq/l, and decreased hematocrit by 5 +/- 1%. These changes were accompanied by a marked decrease in renal nerve activity by 82 + 7%. Urine flow and urinary Na+ excretion increased gradually and peaked at the end of infusion. The innervated kidney excreted 23.3 +/- 3.3 ml urine and 5.5 +/- 0.7 mEq Na+ for the subsequent 60 min. However, the contralateral denervated kidney excreted only 9.5 +/- 2.0 ml urine and 2.2 +/- 0.6 mEq Na+; these values were significantly less than those of the innervated kidney. To examine the role of the sinoaortic and cardiopulmonary baroreceptors and the hepatic nerves in the response of renal nerve activity to the hypertonic NaCl infusion, renal nerve activity was examined in conscious rabbits with sinoaortic baroreceptor denervation (SAD) plus vagotomy and/or section of the anterior and posterior hepatic nerves (SAPH). In rabbits with SAD plus vagotomy or SAPH, the NaCl infusion also decreased renal nerve activity. After combining SAPH and SAD plus vagotomy, the decrease in renal nerve activity was completely blocked. These results indicate that hypertonic NaCl infusion elicits a marked decrease in renal nerve activity which is mediated predominantly by sinoaortic and cardiopulmonary baroreflexes and the hepatic nerves, and that the decrease in renal nerve activity plays an important role in the augmentation of renal function.

Neurons in the caudal ventrolateral medulla mediate the arterial baroreceptor reflex by inhibiting barosensitive reticulospinal neurons in the rostral ventrolateral medulla in rabbits

Participation of the caudal ventrolateral medulla in the arterial baroreceptor reflex was examined in urethane-anesthetized, vagotomized and immobilized rabbits whose aortic nerve was cut bilaterally. The extent of the caudal ventrolateral medulla was mapped by decreases in the renal sympathetic nerve activity and arterial pressure following a local microinjection of a neuroexcitatory amino acid, sodium glutamate (0.075-1.5 nmol). It extended between the levels 1.3 mm rostral and 3.0 mm caudal to the obex. An injection of sodium glutamate into the caudal ventrolateral medulla also diminished spontaneous activity of barosensitive reticulospinal neurons in the rostral ventrolateral medulla. In the 'split medulla preparation' in which the medulla was split along the midsagittal plane to disrupt fiber connections associating both sides, a neurotoxic agent, kainic acid, was injected unilaterally into the rostral ventrolateral medulla. This treatment markedly attenuated responses of renal sympathetic nerve activity and arterial pressure induced by a sodium glutamate injection into the ipsilateral caudal ventrolateral medulla, whereas responses to an injection into the contralateral caudal ventrolateral medulla were totally preserved. In four separate experiments, three to five injections of kainic acid were made unilaterally to cover the whole extent of the caudal ventrolateral medulla. The sympathoinhibitory and depressor responses to stimulation of the ipsilateral aortic nerve were then totally abolished. Simultaneously, the cardiac cycle-related rhythmic fluctuation of renal sympathetic nerve activity, which represented activity of the carotid sinus baroreceptor reflex, was attenuated to the noise level. These results, together with our previous electrophysiological demonstration of barosensitive caudal ventrolateral medulla neurons with axonal projections to the rostral ventrolateral medulla, strongly support the hypothesis that neurons in the caudal ventrolateral medulla mediate the arterial baroreceptor-vasomotor reflex through inhibition of barosensitive reticulospinal neurons in the rostral ventrolateral medulla.

Nicotine impairs reflex renal nerve and respiratory activity in deoxycorticosterone acetate-salt rats.

Smoking exacerbates the increase in arterial pressure in hypertension. The effect of nicotine on the baroreceptor-mediated reflex responses of renal nerve activity (RNA), heart rate, and respiratory activity (minute diaphragmatic activity [MDA]) after bolus injections of phenylephrine was compared in deoxycorticosterone acetate (DOCA)-salt sensitive and normotensive rats. Osmotic minipumps that dispensed either nicotine (2.4 mg/kg/day) or saline were implanted in DOCA and normotensive rats for 18 days. Anesthetized DOCA-nicotine, DOCA-saline, control-nicotine, and control-saline rats had mean arterial pressures (MAP) of 117 +/- 3, 110 +/- 9, 90 +/- 3, and 89 +/- 5 mm Hg, respectively. Nicotine decreased the sensitivity (p less than 0.05) of baroreceptor reflex control of RNA (% delta RNA/delta MAP) in the DOCA-nicotine rats (-0.92 +/- 0.08) compared with the DOCA-saline (-1.44 +/- 0.16), control-nicotine (-1.45 +/- 0.08), or control-saline (-1.45 +/- 0.21) rats. The reflex decrease in respiratory activity (% delta MDA/delta MAP x 100) was impaired (p less than 0.01) in both control-nicotine (-24.5 +/- 3.3) and DOCA-nicotine (-18.2 +/- 4.6) rats compared with control-saline (-59.2 +/- 9.1) and DOCA-saline (-52.5 +/- 9.9) rats. The reflex decrease in heart rate (absolute delta HR/delta MAP) in both DOCA-nicotine (1.56 +/- 0.17) and control-nicotine (1.54 +/- 0.24) rats was augmented compared with DOCA-saline and control-saline rats (0.91 +/- 0.12 and 0.97 +/- 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)