Increase In Renal Nerve Activity Research Articles

Abstract MP23: Arterial Depressor Responses Induced By Neuromodulation Of Deep Peroneal Nerve In Spontaneously Hypertensive Rats

Hypertension affects nearly half of the US population but only 43% achieved blood pressure control with medication alone. Medical devices for hypertension include implantable lead electrodes that stimulate the carotid baroreceptors with promising results, albeit with significant adverse complications. To address these limitations, we have proposed the use of deep peroneal nerve stimulation (DPNS), which elicited a depressor response in anesthetized, breathing supported, spontaneously hypertensive rats (SHR). In this study, we further define the electrical stimulation parameters that optimize the DPNS depressor response, and demonstrated that increasing the pulse duration from 0.15 ms to 1ms, of 1.0 mA pulses at 2 Hz for 10 sec, significantly reduced the mean arterial pressure (MAP) by 8±4 mmHg (p<0.005; n=4) in this animal model. DPNS also caused an immediate increase in renal nerve activity (RNA; p< 0.004, n=5), which may represent afferent sensory axons from the kidney, although this possibility needs to be further investigated. In a separate cohort of anesthetized SHR animals, breathing spontaneously, we demonstrated that optimal DPNS stimulation reduced the MAP from 121±3 to 108±4; p=0.02; n=10). To confirm if DPNS is able to evoke a depressor response in fully awake SHR animals, we developed a novel miniaturized wireless microchannel electrode (w-μCE) with a L-shaped microchannel, through which the DPN slides and locks into a recording/stimulation chamber, causing no discomfort to the animal during locomotion. Two weeks after implantation of the w-μCE neural stimulation device, animals were movement-retrained to received wireless DPNS for 10 min daily for 2 weeks. Blood pressure was measured by tail-cuff at baseline, 10 days after device implantation, and 1 and 2-hr 15 days after DPNS. After two weeks of DPNS, the acute neuromodulation treatment reduced the initial systolic BP of 154±20 mmHg to 127±7 and 119±2 mmHg at 1 and 2 hr; respectively (p< 0.001, n=15-19 measurements; n=2 animals). These results provide evidence of the effectiveness and reliability of DPN neuromodulation as a possible treatment for drug-resistant hypertension.

Taurine Supplementation Inhibits Cardiac and Systemic Renin-Angiotensin System Overactivity After Cardiac Ischemia/Reperfusion in Adult Female Rats Perinatally Depleted of Taurine Followed by High Sugar Intake.

Perinatal taurine depletion and high sugar intake from weaning onward worsen cardiac damage and arterial pressure control after ischemia/reperfusion (IR) in adult male and female rats, which can be ameliorated by high taurine diets or inhibition of renin-angiotensin system. This study tests if taurine supplementation ameliorates cardiac damage and arterial pressure control in adult female rats via alterations of both cardiac and systemic renin-angiotensin system. Female Sprague-Dawley rats were fed normal rat chow and drank water alone (control, C) or water containing 3% beta-alanine (taurine depletion, TD) from conception to weaning, and female offspring were subjected to high sugar intake (normal rat chow and 5% glucose in water; CG and TDG) or the normal rat diet (CW and TDW). At 7weeks of age, half of the rats in each group received 3% taurine in water (CW+T, CG+T, TDW+T, and TDG+T). One week later, rats were subjected to IR or Sham procedures followed by renal nerve recording, plasma and cardiac angiotensin II measurements. Cardiac angiotensin II levels significantly elevated in CG, TDW, and TDG. Further, plasma angiotensin II concentrations were significantly elevated only in the TDG, in consistent with a significant increase in renal nerve activity to juxtaglomerular cells, but not renal vessels and tubules. These abnormalities were ameliorated by short-term taurine supplementation. Thus, in adult female rats that are perinatally depleted of taurine followed by high sugar intake after weaning, taurine supplementation decreases the adverse effects of cardiac IR via inhibition of both cardiac and systemic renin-angiotensin system overactivity.

Neuropeptide specificity of prostaglandin E 2-induced activation of splenic and renal sympathetic nerves in the rat

Sympathetic activation occurs rapidly following intracerebroventricular (icv) injection of prostaglandin E 2 ( PGE 2) . This study examined whether neuropeptides mediate PGE 2-induced sympathetic nerve activation in urethane/chloralose-anesthetized Sprague–Dawley rats. Animals were pretreated (20.0 μg, icv) with the following receptor antagonists; CRF ([ d-Phe 12,Nle 21,38,C α-MeLeu 37]CRF 12–41), AVP-V 1 (Des-Gly-[Phaa 1, d-Tyr(Et) 2,Lys 6,Arg 8]-vasopressin), or OT (OT+V 1, [ d( CH 2) 5, Tyr( Me) 2, Orn 8 ]-vasotocin) followed 20 min later by PGE 2 (2.0 μg, icv). Pretreatment with the CRF antagonist attenuated the increase in renal nerve activity induced by PGE 2 when measured 10 and 30 min post-injection. PGE 2-induced renal nerve activity was also inhibited at both time points by the AVP antagonist and, to a similar extent, the OT antagonist. The AVP antagonist did not effect splenic nerve responses to PGE 2 whereas the CRF antagonist produced an incomplete and transient reduction in PGE 2-induced activation of the splenic nerve. However, the OT antagonist completely blocked the activation of the splenic nerve after central injection of PGE 2. ICV injections of AVP and OT produced immediate changes in splenic and renal nerve activity whereas CRF failed to alter the activity of either nerve in anesthetized or conscious animals. Thus, PGE 2 acts through neuropeptide-specific pathways to initiate sympathetic outflow and OT is a specific component of the sympathetic pathway innervating the spleen.

Estrogen blocks the cardiovascular and autonomic changes following vagal stimulation in ovariectomized rats

The current investigation examines the effect of acute and chronic estrogen administration on baroreflex sensitivity and autonomic tone following 2 h of vagal afferent stimulation in ovariectomized female rats. Female Sprague–Dawley rats were ovariectomized and supplemented daily for 7 days with either estrogen (OVX-E 2; 0.5 μg/kg; s.c.) or saline (OVX-S; 0.9%; s.c.). On the 8th day the animals were anaesthetized (sodium thiobutabarbitol; 100 mg/kg) and instrumented for recording blood pressure, heart rate and efferent vagal and renal nerve activities. The baroreflex was evoked using intravenous injection of various doses of phenylephrine hydrochloride (0.025, 0.05, 0.1 mg/kg). Electrical stimulation of vagal afferents for 2 h produces autonomic imbalance characterized by sympathoexcitation and parasympathetic withdrawal. This protocol of vagal stimulation produced a significant increase in renal nerve activity (from 20±6 to 140±20 spikes/2 s) and decreases in both vagal nerve activity (from 22±3 to 10±2 spikes/2 s) and baroreflex sensitivity (from 0.55±0.05 to 0.3±0.05) in OVX-S female rats. However, vagal stimulation had no effect on baroreflex sensitivity or autonomic nerve activities in OVX-E 2 rats. Administration of a single, bolus dose of estrogen (1×10 −2 mg/kg) to OVX-S rats immediately prior to termination of vagal stimulation blocked the changes in autonomic nerve activities and baroreflex sensitivity previously observed. These results suggest that both chronic and acute estrogen supplementation may provide resistance to the autonomic disturbances associated with visceral afferent activation.

Evidence that activation of central 5-HT(2B) receptors causes renal sympathoexcitation in anaesthetized rats.

The effects of injections i.c.v. of alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine (BW723C86; 0.02 - 2 micromol kg(-1)), a 5-HT(2B) receptor agonist, on renal sympathetic and phrenic nerve activity, mean arterial blood pressure and heart rate were investigated in alpha-chloralose anaesthetized rats pretreated with a peripherally acting 5-HT(2) receptor antagonist. BW723C86 i.c.v. caused a dose-related increase in renal nerve activity reaching a maximum of 67+/-6%, which at the highest dose was associated with a small and maintained fall in mean arterial blood pressure of 7+/-3 mmHg. These changes were not associated with any significant changes in heart rate or phrenic nerve activity. BW723C86-evoked increases in renal nerve activity and hypotension were attenuated by pretreatment (i.c.v.) with SB204741 (300 nmol kg(-1); a 5-HT(2B) receptor antagonist) but not by the same dose (i.c.v.) of ketanserin (a 5-HT(2A) receptor antagonist) or RS102221 (a 5-HT(2C) receptor antagonist). None of these antagonists alone had any effect on the variables being measured. It is concluded that central 5-HT(2B) receptors may play a selective role in the control of sympathetic supply to the kidney, which could be important in the central mechanisms involved in blood volume regulation. British Journal of Pharmacology (2000) 129, 177 - 183

Visceral afferent activation-induced changes in sympathetic nerve activity and baroreflex sensitivity.

The following experiments were done to determine whether changes in baroreflex sensitivity evoked by cervical vagus nerve stimulation are due to sympathoexcitation mediated by the parabrachial nucleus. The relative contribution of cardiopulmonary and general gastric afferents within the cervical vagus nerve to the depression in baroreflex sensitivity are also investigated. Male Sprague-Dawley rats anesthetized with thiobutabarbital sodium (50 mg/kg) were instrumented to measure blood pressure and heart rate or for the continuous monitoring of renal sympathetic nerve activity. Baroreflex sensitivity was measured using bolus injections of phenylephrine. Electrical stimulation of the cervical vagus (with or without the aortic depressor nerve) or the abdominal vagus nerve produced a significant increase in renal nerve activity and a decrease in baroreflex sensitivity. Both of these effects were blocked after the microinjection of lidocaine into the parabrachial nucleus before nerve stimulation. Therefore, we conclude that an increase in the activity of cardiac, pulmonary, or general gastric afferents mediated the increased sympathetic output and decreased baroreflex sensitivity via a pathway involving the parabrachial nucleus.

Functional response to graded increases in renal nerve activity during hypoxia in conscious rabbits.

Changes in renal sympathetic nerve activity (SNA) are postulated to influence renal function in selective ways, such that different levels of activation produce particular renal responses, initially in renin release, then sodium excretion, with changes in renal hemodynamics occurring only with much greater stimulus intensities. The aim of this study was to determine the renal hemodynamic and excretory responses to graded physiological increases in renal SNA induced by breathing different hypoxic gas mixtures. Experiments were performed in seven conscious rabbits subjected to four gas mixtures (14% O2, 10% O2, 10% O2 + 3% CO2, and 10% O2 + 5% CO2) and instrumented for recording of renal nerve activity. After a 30-min control period, rabbits were subjected to one of the four gas mixtures for 30 min, and then room air was resumed for a further 30 min. The four gas mixtures increased renal SNA by 14, 38, 49, and 165% respectively, but arterial pressure (thus renal perfusion pressure) was not altered by any of the gas mixtures. The greatest level of sympathetic activation produced significant falls in glomerular filtration rate (GFR), renal blood flow, sodium and fluid excretion, and significant increases in plasma renin activity. These returned to levels not significantly different from control conditions in the 30-min period after the gas mixture. When the changes to the various gas mixtures were analyzed within each rabbit, a significant linear relationship was found with all variables to the increase in SNA. Renal denervation in a separate group of seven rabbits completely abolished all of the above responses to the different gas mixtures. Thus graded activation of renal nerves induced by changes in inspired gas mixtures resulted in graded decreases in renal blood flow, GFR, and sodium excretion and graded increases in renin activity, with the changes occurring across a similar range of nerve activities; there was no evidence for a selective change in any renal variable.

Impact of Systemic Depulsation on Tissue Perfusion and Sympathetic Nerve Activity

Background. We postulated that pathophysiologic processes under nonpulsatile circulation are related to the behavior of the sympathetic nerve activity that regulates tissue perfusion. Methods. Pulsatile and nonpulsatile pumps were installed in parallel in the left heart bypass circuit of anesthetized goats (n = 9) so that pulsatile circulation could be converted to nonpulsatile circulation instantly. At 5 minutes before and after systemic depulsation, we measured hemodynamic indices, renal nerve activity, and regional blood flow of the brain, heart, and renal cortex. Results. Renal nerve activity was significantly elevated after systemic depulsation (15.6 ± 9.3 versus 19.4 ± 9.8 μV), when mean aortic pressure remained almost constant. The renal cortical flow was significantly reduced after depulsation (3.61 ± 1.23 versus 2.93 ± 1.19 mL · min −1 · g −1), whereas no significant difference was found in the regional blood flow of the brain or the heart. Conclusions. The significant reduction of renal cortical blood flow after systemic depulsation is associated with a significant increase in renal nerve activity. Our results suggest that increased renal nerve activity plays an important role in the reduction of renal function after systemic depulsation.

A comparison of the effects of doxazosin and terazosin on the spontaneous sympathetic drive to the bladder and related organs in anaesthetized cats

The effects of i.v. infusion of the α 1-adrenoceptor antagonists doxazosin and terazosin (2 mg kg −1 h −1) on spontaneous hypogastric, renal and inferior cardiac nerve activity, spontaneous bladder contractions, blood pressure, heart rate and femoral arterial flow were investigated separately in α-chloralose-anaesthetized cats. Both drugs caused a reduction in hypogastric nerve activity associated with no overt changes in spontaneous bladder contractions. Doxazosin was more potent than terazosin, in that there was a significant reduction in hypogastric nerve activity after 20 min (0.67 mg kg −1) of infusion, while for terazosin this occurred after 40 min (1.33 mg kg −1). Both drugs also caused significant falls in blood pressure of 34 ± 3 mm Hg and 33 ± 4 mm Hg after 60 min. This was associated with no change in heart rate for doxazosin while terazosin caused an initial and significant increase in heart rate of 20 ± 3 beats min −1 by 5 min, declining by 30 min to 1 ± 5 beats min −1. This terazosin-induced tachycardia was associated with a significant increase in cardiac nerve activity of 128 ± 22%. Both drugs caused increases in renal nerve activity however only for doxazosin was this increase significant. Femoral arterial conductance was also increased by both drugs, however, for doxazosin this increase was immediate and larger over the infusion period. These results demonstrate that α 1-adrenoceptor antagonists can reduce sympathetic drive to the bladder and related organs.

Neural effects on renal blood flow during acute hypotension vary with antihypertensive drugs.

To examine the neural effects of antihypertensive drugs on renal blood flow, we measured blood flow and renal sympathetic nerve activity simultaneously in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to two days after surgery, intravenous administration of manidipine (calcium antagonist, n = 10), doxazosin (alpha 1-adrenergic receptor antagonist, n = 9), and clonidine (n = 7) lowered mean arterial pressure by at least 20% from baseline levels. Manidipine initiated a reduction of renal blood flow when mean pressure decreased by 20 +/- 2 mm Hg. At the maximal decrease in renal blood flow (mean pressure, -33 +/- 2 mm Hg), percent decrease in flow (-27 +/- 2%) significantly correlated with percent increase in renal nerve activity (+205 +/- 40%, r = -.878). Doxazosin began to decrease renal blood flow at a level of arterial pressure similar to that in manidipine treatment, whereas the maximal decrease in flow (-19 +/- 2%; mean pressure, -33 +/- 2 mm Hg; nerve activity, +225 +/- 44%) was significantly less than that in manidipine treatment. Although clonidine decreased arterial pressure and renal nerve activity, renal blood flow did not decrease even at the maximal decrease in mean pressure of 29 +/- 1 mm Hg. The addition of clonidine to manidipine treatment suppressed reflexly enhanced renal nerve activity and restored blood flow to the pretreatment level despite pronounced hypotension. These results clearly demonstrate that antihypertensive drugs with blocking action on renal nerve activity are capable of maintaining renal blood flow and that those associated with reflex-induced enhancement of nerve activity exert deteriorating effects on renal blood flow. Furthermore, a decrease in renal blood flow induced by calcium antagonists is mainly attributed to reflexly enhanced renal nerve activity.

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.

Effects of chemoreceptor stimulation by almitrine bismesylate on renal function in conscious rats.

A possible link between chemoreceptor activity and kidney function has been demonstrated by several groups (Bardsley and Suggett 1987, Bardsley et al. 1991, Behm et al. 1992, Karim et al. 1987, Honig et al. 1985, Honig 1989, Schmidt et al. 1985). Most of these studies were performed in anaesthetized animals and led to conflicting results with marked differences between hypoxic and pharmacological chemoreceptor stimulation. Hypoxic stimulation of the vascularly isolated carotid bodies resulted in an increase in renal nerve activity (Linden et al. 1981), and in decreases in glomerular filtration rate (GFR), renal blood flow (RBF) and increase in tubular sodium reabsorption (Karim et al. 1987). After sectioning of the renal nerves the same type of chemoreceptor stimulation caused an increase in urinary water and sodium excretion. This shows that the chemoreceptors in the carotid bodies mediate reflex effects on renal function in two ways, one dependent on renal nerves and the other one on the release of one or more hormones. In intact conscious animals it is likely that hypoxic chemoreceptor stimulation activates the neuronal sympathetic pathway thereby masking the humoral axis. As a net result there is antidiuresis and antinatriuresis (Behm 1991).KeywordsSham OperateMean Arterial Blood PressureCarotid BodyRenal NerveTubular Sodium ReabsorptionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Ganglionic blockade with tetraethylammonium in conscious rats.

The sympathetic ganglionic blocking agent tetraethylammonium has been used as a clearance marker for the measurement of renal plasma flow, but the sympathetic ganglionic blocking dose in rats is unknown. In light of differential reflex activation of sympathetic nerve activity to heart and kidney, we compared the effect of tetraethylammonium on renal nerve activity, mean arterial pressure, and heart rate. Conscious rats were infused with either vehicle (isotonic saline) or tetraethylammonium (n = 7 in both groups). Tetraethylammonium was infused cumulatively (35 minutes per dose) in the following doses: 10(-5), 10(-4), 10(-3), 10(-2), and 10(-1) g/kg body wt per hour. Doses for 15% reduction were 10(-1) for mean arterial pressure, 0.55 x 10(-1) for heart rate, and 0.055 x 10(-1) g/kg body wt per hour for renal nerve activity. Renal nerve activity was abolished at 10(-1) g/kg body wt per hour; mean arterial pressure and heart rate were unchanged at doses lower than 10(-1) g/kg body wt per hour. The lethal dose was 1 g/kg body wt per hour. No changes were observed in vehicle-treated animals. Tetraethylammonium at 10(-1) g/kg body wt per hour resulted in an attenuated increase in renal nerve activity during acetylcholine-induced reduction in mean arterial pressure, reflecting arterial baroreceptor inhibition. We conclude that renal nerve activity is 10- and 18-fold more sensitive to sympathetic ganglionic blockade than heart rate and mean arterial pressure, respectively. When tetraethylammonium is used as a clearance marker for measurement of renal plasma flow in rats, it should be administered in doses less than 10(-2) g/kg body wt per hour.

Selective preglomerular constriction to nerve stimulation in rat hydronephrotic kidneys.

The purpose of this study was to quantitate the constrictor responses of pre- vs. postglomerular microvessels during brief increases in renal nerve activity by directly observing the intact microcirculation. To validate the use of the rat hydronephrotic kidney model for this purpose, the vascular reactivity of hydronephrotic kidneys, and normal kidneys was assessed to adrenergic and neural stimulation by quantitating whole kidney blood flow velocity changes elicited by intravenous administration of norepinephrine, electrical stimulation of the posterior hypothalamus, and direct renal nerve stimulation. Hydronephrotic and nonhydronephrotic kidneys responded comparably to norepinephrine and posterior hypothalamic stimulation; however, the hydronephrotic kidneys were less responsive than normal kidneys to direct renal nerve stimulation. In the microcirculatory experiments, stimulation of the splanchnic nerve (2-8 Hz) induced a frequency-dependent constriction of interlobular arteries and afferent arterioles. Preglomerular vessel diameters decreased by 42-53% during the 8-Hz stimulation, whereas the efferent arteriolar diameters did not significantly change. Thus, constriction of preglomerular vessels mediates, in large part, the changes in renal hemodynamics evoked by increases in renal sympathetic nerve activity.

Acute effect of hypobaria and hypoxia on renal nerve activity in anaesthetized rabbits.

To determine the acute effect of reduced barometric pressure and hypoxia on renal nerve activity, urethane-anaesthetized and mechanically ventilated rabbits were randomly exposed to the following four separate conditions in a decompression chamber: hypoxic hypobaria (n = 7), hypoxic normobaria (n = 5), normoxic hypobaria (n = 8) and slow normoxic hypobaria (n = 7). A combination of rapid decompression and simultaneous adjustment of inspired PO2 was used to simulate an altitude of 6600 m, and renal nerve activity and haemodynamics, such as systemic blood pressure and heart rate, were measured. During both hypoxic hypobaria and hypoxic normobaria, there were significant and similar increases in renal nerve activity at 6600 m (54 +/- 7% and 61 +/- 13% from each baseline, respectively). However, there were no changes in renal nerve activity during normoxic hypobaria or slow normoxic hypobaria with decompression rates of 1000 or 400 m min-1, respectively. From these results, we conclude that a reduction in barometric pressure without hypoxia does not affect renal nerve activity in anaesthetized rabbits.

Differential control of sympathetic activity to kidney and skeletal muscle by ventral medullary neurons

A rise in arterial blood pressure can be evoked by microinjections of d,l-homocysteic acid into localized regions of the ventrolateral medulla of the cat. Three patterns of sympathetic discharge can be identified during the pressor response. A differential pattern consisting of an increase in renal nerve activity and no change in sympathetic activity to skeletal muscle vasculature can be elicited from sites ventromedial to the caudal pole of the facial nucleus. From more lateral and caudal sites, a generalized sympatho-excitation is evoked in the outflow to both the kidney and hindlimb muscle vasculature. A third response consisting of a differential increase in muscle sympathetic activity simultaneous with a small decrease in renal nerve activity could be evoked from caudal sites, lateral to the inferior olives and superficial to the ventral surface. The results show that ventral medullary neurons can selectively activate sympathetic outflow to control specific vascular beds. These data may support the hypothesis that the ventrolateral medulla contains discrete groups of topographically arranged neurons that can differentially control sympathetic tone to various end-organs.

Contribution of baroreceptor reflexes to blood pressure and sympathetic responses to cholecystokinin and vasoactive intestinal peptide in anesthetized dogs

The effects of synthetic vasoactive intestinal peptide (VIP) and cholecystokinin (CCK) on systemic blood pressure and renal nerve activity were studied before and after cervical vagotomy, and sino-aortic denervation with vagotomy in anesthetized dogs. Intravenous injection of VIP (5 μg/kg) in animals with an intact neuraxis produced a significant decrease in systemic blood pressure and a significant increase in renal nerve activity. These responses to VIP did not change after vagotomy and after complete denervation, VIP did not cause any change in renal nerve activity, even during hypotension. The level of hypotension after complete denervation was greater than that under other conditions. These results indicate that the cardiovascular effects of VIP are reduced by activation of the systemic baroreceptors. Intravenous injection of CCK (10 μg/kg) in animals with an intact neuraxis produced significant decreases in blood pressure and renal nerve activity. These responses to CCK were abolished in animals with cervical vagotomy only. However, following complete denervation of the carotid sinus and total section of the vagal nerves, CCK caused a significant increase in blood pressure and renal sympathetic nerve activity. These results indicate that the sympathetic depressor effect of CCK may be mediated by activation of the vagal afferent, and that the sympathetic pressor effect may be due to a direct action of CCK on the central nervous system. Thus, each gastrointestinal peptidde may regulate the cardiovascular system through a different mechanism.

Mechanism of inhibition of renin response to hypotension by atrial natriuretic factor

We have reported that infusion of atrial natriuretic factor (ANF) inhibited the rise in plasma renin activity (PRA) in response to constriction of the abdominal aorta to cause a reduction in renal perfusion pressure (RPP). To evaluate the effect of ANF on neural control of renin release, acute thoracic inferior vena caval constriction (TIVCC) was performed in conscious dogs to reduce arterial pressure by 25% of control and stimulate PRA by a reflex increase in renal nerve activity and a reduction in RPP. Propranolol was used to block neural stimulation of renin release. TIVCC caused significant increases in PRA, plasma aldosterone, arginine vasopressin (AVP), and adrenocorticotropic hormone (ACTH) concentrations. The increase in PRA was significantly reduced by the infusion of either ANF at 20 ng.kg-1.min-1 or propranolol. The combined infusion of ANF and propranolol produced an additive and complete inhibition of the renin response to TIVCC; therefore the effect of ANF is independent of neural stimulation of renin release. ANF at 20 ng.kg-1.min-1 also inhibited increases in aldosterone, AVP, and ACTH, but ANF at 5 ng.kg-1.min-1 only affected the aldosterone response to TIVCC. Therefore ANF inhibits angiotensin II-stimulated aldosterone synthesis and/or secretion at very low doses and at higher doses attenuates reflex increases in AVP and ACTH caused by hypotension.

Stimulation of renal sympathetic activity by static contraction: evidence for mechanoreceptor-induced reflexes from skeletal muscle.

Static muscular contraction in anesthetized animals has been firmly established to reflexly increase arterial pressure. Although group III and IV muscle afferents are known to be responsible for this reflex pressor response, there is no evidence that the stimulation of muscle mechanoreceptors, many of which are supplied by group III fibers, plays a role in causing this contraction-induced reflex effect. To provide this evidence, we recorded renal sympathetic nerve activity in chloralose-anesthetized cats while contracting the triceps surae muscles. We found that static contraction tripled renal nerve activity within three seconds of its onset, an increase that was abolished by cutting the L6 and S2 dorsal roots. On average, the contraction-induced increase in renal nerve activity was observed 0.8 +/- 0.1 seconds after the onset of this maneuver. In addition, intermittent tetanic contractions synchronized renal nerve discharge so that a burst of activity was evoked by each contraction. A similarly synchronized renal nerve discharge was evoked in paralyzed cats by electrical stimulation of the tibial nerve at five times motor threshold, a current intensity that activates group III afferents. We conclude that, in anesthetized animal preparations, mechanoreceptors with group III afferents contribute to the reflex stimulation of renal sympathetic outflow evoked by muscular contraction.

Reflex increase in renal nerve activity during acutely altered portal venous pressure

This study was designed to determine the reflex effects of renal nerve activity during acutely altered portal venous pressure in anesthetized dogs. Following inflation of a balloon in the main portal vein of animals with the neuraxis intact, mean blood pressure (MBP) fell significantly from 127 ± 8 mm Hg to 101 ± 7 mm Hg, while renal nerve activity (RNA) increased to 189 ± 11%. This significant increase in RNA during inflation of the balloon was not entirely eliminated by either carotid sinus nerve (CSN) denervation (163 ± 9% of the control level) or vagotomy (161 ± 11% of the control level). The reflex increase in RNA observed with the combined denervation of the carotid sinus and vagal nerves (CSN + Va denervation) was 138 ± 2% of the control level, and this level of RNA increase was significantly smaller compared to those in the other 3 groups (intact, CSN or Va denervated). Even when the portal venous pressure below caudal to the balloon was controlled at a pre-distension level by means of opening an artificial bypass constructed between the mesenteric vein and the femoral vein in the CSN + Va denervated group, the increased RNA response during inflation of the balloon remained. After hepatic denervation in the CSN + Va denervated group with the opening of the bypass, however, inflation of a balloon caused no significant changes in RNA, even when more profound hypotension existed during inflation of the balloon. The results of this study indicate that the increase in RNA induced by acute occlusion of the portal vein can be explained by at least two neural reflex mechanisms; the systemic baroreceptor reflex and the hepato-portal mechanoreceptor reflex. A decrease in mechanoreceptor activity produced augmented renal nerve activity.