Biomedical subjects

S Y Jones

Publications and source records attributed to S Y Jones.

36 records · Page 2Linked to original sources

PubMed1995

Analysis of renal sympathetic nerve responses to stress.

We studied sympathetic nerve activity responses to acute environmental stress (air jet stress) in conscious Wistar-Kyoto, spontaneously hypertensive, and borderline hypertensive rats. The borderline hypertensive rats were fed either 1% (normotensive) or 8% (hypertensive) NaCl. Renal sympathetic nerve activity responses were analyzed with three methods: mean integrated voltage over time, power spectrum analysis, and sympathetic peak detection analysis. Measurements of mean integrated voltage over time showed that air jet stress increased renal sympathetic nerve activity in spontaneously hypertensive rats and in borderline hypertensive rats on 8% NaCl but not in the other groups. In the NaCl responders, power spectrum analysis of renal sympathetic nerve activity indicated that the increase in relative power was at the heart rate frequency, indicating that it was related to renal sympathetic nerve discharge coupled to the cardiac cycle. Sympathetic peak detection analysis of renal sympathetic nerve activity indicate that there was an increase in frequency of sympathetic peaks of greater height and shorter duration because of sinoaortic baroreceptor deactivation (increased peak frequency) and the recruitment of more active fibers (greater peak height) firing with greater synchronization (shorter peak duration). Additional methods of analysis of renal sympathetic nerve activity provide information in addition to that derived from measurement of mean integrated voltage over time.

Animals↗

PubMed1995

Cardiopulmonary baroreflex function in nephrotic rats.

Efferent renal sympathetic nerve activity is increased in experimental nephrotic syndrome and exhibits attenuated cardiopulmonary baroreflex inhibition during volume expansion in anesthetized rats. Additional studies were performed in conscious rats to avoid the potentially confounding influences of anesthesia; these studies used another more specific standardized stimulus for cardiopulmonary baroreflex activation. Sprague Dawley rats were studied 3 to 4 wk after adriamycin injection (3.5 mg/kg iv); all rats developed proteinuria. In sinoaortic denervated rats (anesthetized), graded frequency stimulation of the central end of the cut right vagus nerve produced frequency-dependent decreases in mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity. The decreases in mean arterial pressure and heart rate were similar in control and nephrotic rats, but efferent renal sympathetic nerve activity decreased significantly less in nephrotic than control rats over the entire frequency range (P < 0.02). In sinoaortic denervated rats (conscious), 10% body weight isotonic saline volume expansion decreased mean arterial pressure, heart rate, and efferent renal sympathetic nerve activity. The decreases in mean arterial pressure and heart rate were similar in control and nephrotic rats, but efferent renal sympathetic nerve activity decreased significantly less in nephrotic than control rats over the entire period of volume expansion (P < 0.04). In nephrotic syndrome, the cardiopulmonary baroreflex inhibition of efferent renal sympathetic nerve activity is decreased; the defect lies in the central portion of the reflex. This may contribute to the observed increase in efferent renal sympathetic nerve activity in nephrotic syndrome.

Animals↗

PubMed1995

Acute environmental stress overrides cardiac volume receptor reflex in borderline hypertensive rats.

OBJECTIVE: To examine whether acute environmental stress (air-jet stress) modulates the exaggerated natriuresis to volume expansion in conscious borderline hypertensive rats. DESIGN: Intravenous isotonic saline volume expansion was performed with and without superimposed acute air-jet stress in conscious borderline hypertensive rats which had consumed a 1% NaCl diet (normotensive) or an 8% NaCl diet (hypertensive) for 12 weeks. METHODS: Conscious rats were instrumented for measurement of arterial pressure, renal sympathetic nerve activity and collection of bladder urine. RESULTS: Arterial pressure was greater in the 8% NaCl borderline hypertensive rats than in the 1% NaCl borderline hypertensive rats. In the absence of acute air-jet stress the 8% NaCl borderline hypertensive rats exhibited exaggerated natriuresis and exaggerated inhibition of renal sympathetic nerve activity compared with the 1% NaCl borderline hypertensive rats. Acute air-jet stress increased both arterial pressure and renal sympathetic nerve activity reversibly, and attenuated natriuresis in the 8% NaCl but not in the 1% NaCl borderline hypertensive rats. CONCLUSION: Acute environmental stress (air-jet stress) attenuates exaggerated natriuresis in hypertensive but not in normotensive borderline hypertensive rats via increased renal sympathetic nerve activity.

Acute Disease↗

PubMed1995

Mechanisms of exaggerated renal sympathoinhibition during volume loading in spontaneously hypertensive rats.

OBJECTIVE: This investigation examined the central portion of the cardiac volume receptor reflex, which mediates the exaggerated renal sympathoinhibitory response to isotonic saline volume loading observed in spontaneously hypertensive rats, and compared the findings with those in normotensive Wistar-Kyoto control rats. DESIGN: Wistar-Kyoto and spontaneously hypertensive rats were fed either a normal diet or one high in sodium chloride for 4 weeks and subjected to sinoaortic denervation. To evaluate the central gain of the cardiopulmonary baroreflex, electrical stimulation of the central portion of the cut vagus was used to provide a standardized stimulus that simulates activation of cardiac volume receptors. To evaluate central alpha 2-adrenoceptor regulation of renal sympathetic nerve activity, volume loading was performed in rats pretreated with intracerebroventricular guanabenz, which decreased the elevated basal values of arterial pressure, heart rate and renal sympathetic nerve activity in spontaneously hypertensive rats towards those of Wistar-Kyoto rats. RESULTS: Vagal stimulation produced frequency-dependent decreases in arterial pressure, heart rate and renal sympathetic nerve activity that were similar in the two strains of rats on either a normal- or a high-sodium diet. Volume administration in rats pretreated with guanabenz resulted in similar decreases in renal sympathetic nerve activity in the two strains of rats. CONCLUSIONS: The mechanism of exaggerated renal sympathoinhibition during volume administration in spontaneously hypertensive rats involves an alteration in central alpha 2-adrenoceptor regulation of renal sympathetic nerve activity.

Animals↗

PubMed1994

Hemodynamics and baroreflex function in rats with nephrotic syndrome.

The excess renal sodium retention leading to edema formation in the nephrotic syndrome (NS) is substantially dependent on increased efferent renal sympathetic nerve activity (RSNA). This study examined whether the hypoalbuminemia in NS is reflected as a decrease in cardiac output or cardiac function and whether the increased RSNA in NS is due to alterations in arterial and/or cardiopulmonary baroreflex function. NS was induced in rats with adriamycin (3.5 mg/kg i.v.), and they were studied 4 wk after injection. Mean arterial pressure (MAP) was similar in control (C) and NS rats. Cardiac indexes (CIs; cardiac output/body wt) were 29 +/- 1 and 26 +/- 1 ml.min-1.100 g-1 in C and NS rats, respectively. Total peripheral resistance indexes were significantly greater in NS than in C rats (4.7 +/- 0.2 vs. 4.1 +/- 0.1 mmHg.100 g.min.ml-1). Cardiac function during increases in cardiac filling pressure was not different between C and NS rats. The afferent limb of the arterial baroreflex was assessed by measuring aortic depressor nerve activity (ADNA) while the efferent limb was assessed by measuring RSNA in C and NS rats during increases in MAP. The central component of the arterial baroreflex was assessed from plots of RSNA (output) vs. ADNA (input). Comparisons between C and NS rats before and after vagotomy revealed no differences in the gains of any component of the arterial baroreflex. The cardiopulmonary baroreflex was assessed in a similar manner by measuring afferent vagus nerve activity (VGNA) and efferent RSNA during volume expansion before and after sinoaortic denervation (SAD). Before SAD, gains were similar in C and NS rats. After SAD, gains of the total (-1.59 +/- 0.44 vs. -3.64 +/- 0.65%/mmHg) and the central/efferent limb (-0.26 +/- 0.07 vs. -0.67 +/- 0.14 %/%) were significantly reduced (P < 0.05) in NS compared with C rats while the gain of the afferent limb of the reflex was similar in C and NS rats. These results indicate that NS rats with significant hypoalbuminemia maintain an arterial pressure similar to C rats by increasing total peripheral resistance, which serves to offset the tendency to a lower CI. Arterial baroreflex function in NS does not differ from that in C, but decreased cardiopulmonary baroreflex inhibition of RSNA in NS may contribute to the increased RSNA.

Animals↗

PubMed1994

Role of endogenous peripheral opioid mechanisms in renal function.

The role of endogenous peripheral opioid mechanisms in renal function was evaluated in normotensive and hypertensive rats. Intravenous naloxone methylbromide, a quaternary opioid antagonist with limited ability to cross the blood-brain barrier, was used to inhibit endogenous peripheral opioid mechanisms. In normotensive rats, the opioid antagonist impaired the normal renal adaptive response to dietary sodium restriction. In spontaneously hypertensive rats, the opioid antagonist did not affect the renal functional responses to acute environmental stress. These data indicate that, depending on the nature of the intervention, a role for endogenous peripheral opioid mechanisms in the renal function responses may be identified.

Acute Disease↗

PubMed1993

Cardiac volume receptor reflex in borderline hypertensive rats.

With increased dietary NaCl intake (8% NaCl), borderline hypertensive rats (BHR) develop hypertension and exhibit an exaggerated natriuresis in response to intravenous isotonic saline volume expansion. The exaggerated natriuresis is mediated by the concurrent exaggerated withdrawal of efferent renal sympathetic nerve activity since prior renal denervation eliminates the exaggerated natriuretic response. It was the objective of the present study to examine cardiac volume receptor reflex control of efferent renal sympathetic nerve activity in BHR made hypertensive by increased dietary NaCl intake. BHR were fed either 1% or 8% NaCl from age 4 to 16 weeks. BHR fed 8% NaCl were hypertensive (148 +/- 9 mmHg) compared with BHR fed 1% NaCl (115 +/- 6 mm Hg, p < 0.05). In one protocol, measurements of right atrial pressure and efferent renal sympathetic nerve activity were made in sinoaortic-denervated BHR before and during a 10% body weight intravenous isotonic saline volume load. Compared with 1% NaCl BHR, 8% NaCl BHR showed both a greater maximal inhibition of efferent renal sympathetic nerve activity (-67 +/- 4% versus -31 +/- 3% of control, p < 0.05) and gain (-22.0 +/- 2.3 versus -9.7 +/- 1.7%/mm Hg, p < 0.05). In a second protocol, measurements of efferent renal sympathetic nerve activity were made in sinoaortic-denervated BHR before and during graded frequency stimulation of the central portion of the sectioned vagus nerve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effect of acute NaCl depletion on NaCl-sensitive hypertension in borderline hypertensive rats.

OBJECTIVES: The borderline hypertensive rat (BHR) is the first generation offspring of a mating between a female spontaneously hypertensive rat and a male normotensive Wistar-Kyoto rat. With increased dietary NaCl intake, the BHR develops hypertension and augmented cardiovascular and renal responses to acute environmental stress. This investigation sought to examine the role of extracellular fluid volume (ECFV) in these changes. DESIGN: Three groups of 16-week-old BHR were studied: (1) rats on a 1% NaCl diet for 12 weeks; (2) rats on an 8% NaCl diet for 12 weeks; and (3) rats on an 8% NaCl diet for 12 weeks plus furosemide (50 mg/kg, i.p., twice daily) for the preceding 2 days. METHODS: Rats were chronically instrumented for the measurement of mean arterial pressure (MAP), heart rate and renal hemodynamic, excretory and sympathetic nerve activity responses to acute environmental stress (acute air jet stress). ECFV was measured as inulin space. RESULTS: BHR fed an 8% NaCl diet had increased MAP, urinary sodium excretion and ECFV compared with those fed a 1% NaCl diet; they also exhibited augmented pressor, tachycardic, renal sympathetic nerve excitatory and antinatriuretic responses to acute environmental stress. When 8% NaCl-diet BHR were treated with furosemide for 2 days, arterial pressure, urinary sodium excretion, ECFV and cardiovascular and renal responses to acute environmental stress returned to values seen in 1% NaCl-diet BHR. CONCLUSIONS: The hypertension and increased cardiovascular and renal responses to acute environmental stress produced by increased dietary NaCl intake in BHR derive from a central nervous system site of action via a mechanism(s) related to ECFV and/or sodium.

Animals↗

PubMed1992

Arterial baroreceptor reflex function in borderline hypertensive rats.

With increased dietary NaCl intake (8% NaCl), the borderline hypertensive rat develops hypertension, thus expressing the phenotype of the spontaneously hypertensive parent. Since arterial baroreceptor reflex function is impaired in the spontaneously hypertensive parent, it was the objective of this study to examine arterial baroreceptor reflex function in the borderline hypertensive rat made hypertensive by increased dietary NaCl intake. Borderline hypertensive rats were fed either 1% or 8% NaCl from age 4 to 16 weeks. Borderline hypertensive rats fed 8% NaCl (n = 10) were hypertensive compared with borderline hypertensive rats fed 1% NaCl (n = 11) (141 +/- 3 versus 120 +/- 4 mm Hg, p less than 0.01). They were chronically instrumented for the recording of arterial pressure, heart rate, and renal sympathetic nerve activity. The percent change from control in heart rate and renal sympathetic nerve activity resulting from increases (phenylephrine) and decreases (nitroglycerine) in arterial pressure were measured in conscious freely moving animals. With respect to arterial baroreceptor reflex control of heart rate, 8% NaCl borderline hypertensive rats had a similar range (75 +/- 4%) and maximal gain (-2.72 +/- 0.24%/mm Hg) as 1% NaCl borderline hypertensive rats (70 +/- 4%; -2.78 +/- 0.50%/mm Hg). With respect to arterial baroreceptor reflex control of renal sympathetic nerve activity, 8% NaCl borderline hypertensive rats had values for range (205 +/- 22%) and maximal gain (-3.92 +/- 0.93%/mm Hg) that were not significantly different from those for 1% NaCl borderline hypertensive rats (167 +/- 33%, -2.76 +/- 0.62%/mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effect of dietary potassium chloride in borderline hypertensive rats.

The borderline hypertensive rat is the first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto rat. With increased dietary sodium chloride intake, the borderline hypertensive rat develops hypertension and exaggerated cardiovascular and renal responses to acute environmental stress, similar to those observed in the hypertensive spontaneously hypertensive rat parent. In other models of sodium chloride-sensitive hypertension with different genetic background (Dahl rat), dietary potassium chloride supplementation protects against the development of hypertension, increased sympathetic nervous system activity, and exaggerated responses to acute environmental stress. This investigation sought to determine whether the dietary sodium chloride-induced development of both the hypertension and the exaggerated responses to acute environmental stress could be reversed or prevented by increased dietary potassium chloride intake. Dietary potassium chloride intake was increased with a 1% potassium chloride drinking solution either after 12 wk of 8% sodium chloride intake (reversal) or concomitant with the onset of 12 wk of 8% sodium chloride intake (prevention). An increase in dietary potassium chloride intake did not reverse or prevent the development of either the hypertension or the exaggerated cardiovascular and renal responses to acute environmental stress in borderline hypertensive rats fed 8% sodium chloride. It is concluded that the difference in genetic background between borderline hypertensive rats and other models of sodium chloride-sensitive hypertension is an important determinant of the protective effect of dietary potassium chloride supplementation.

Animals↗

PubMed1991

Renal mu opioid receptor mechanisms in regulation of renal function in rats.

Studies were performed in pentobarbital anesthetized Sprague-Dawley rats to determine whether mu opioid receptor agonists produce changes in renal function via intrarenal mechanisms. Left renal artery infusion of isotonic saline vehicle or the selective mu opioid receptor agonist, dermorphin (0.5 nmol/kg/min), did not alter mean arterial pressure or heart rate. In contrast, left renal artery dermorphin administration produced a significant decrease in left kidney urinary flow rate and sodium excretion without altering glomerular filtration rate or effective renal plasma flow; function of the right kidney was unaffected. Pretreatment of the left kidney with the opioid receptor antagonist naloxone, 50 micrograms/kg into left renal artery, prevented changes in urinary flow rate and sodium excretion induced by subsequent left renal artery dermorphin administration. Prior bilateral renal denervation abolished the antidiuretic and antinatriuretic responses to left renal artery dermorphin administration. These results suggest that mu opioid receptor agonists participate in the process of renal tubular sodium and water reabsorption via an intrarenal action that is dependent on an interaction with renal sympathetic nerves. This may occur via an action of mu opioid receptor agonists to facilitate the nerve terminal release and/or the direct tubular action of norepinephrine to affect renal tubular sodium and water reabsorption.

Analgesics, Opioid↗

PubMed1991

Central alpha 2-adrenoceptor responsiveness in borderline hypertensive rats.

Increased dietary NaCl intake increases the responsiveness of central nervous system alpha 2-adrenoceptors which regulate the neural control of renal function in spontaneously hypertensive rats (SHR) but not Wistar-Kyoto (WKY) normotensive rats. The borderline hypertensive rat (BHR) is the first filial offspring of the SHR and the WKY. With increased dietary NaCl intake, the BHR develops hypertension and expresses other characteristics of the hypertensive SHR parent. This investigation sought to determine whether increased dietary NaCl intake in the BHR enhances the responsiveness of central nervous system alpha 2-adrenoceptors. Six weeks of increased dietary NaCl intake (8% versus 1% NaCl) in BHR augmented the depressor, bradycardic, renal sympatho-inhibitory and diuretic responses to intracerebroventricular administration of graded doses (5, 25 and 125 micrograms) of the alpha 2-adrenoceptor agonist, guanabenz. The results suggest that the potential for an increased responsiveness of central nervous system alpha 2-adrenoceptors is genetically transmitted to the BHR by the SHR and may be exposed in the BHR by increased dietary NaCl intake.

Animals↗

PubMed1991

Renal manifestations of NaCl sensitivity in borderline hypertensive rats.

Compared with the normotensive Wistar-Kyoto rat, the spontaneously hypertensive rat exhibits exaggerated alterations in renal sympathetic nerve activity and excretory function during volume expansion (exaggerated natriuresis) and environmental stress (antinatriuresis). The borderline hypertensive rat is the first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto rat and develops hypertension with increased dietary NaCl intake. The present investigation sought to determine whether the dietary NaCl intake-induced transition from the normotensive state of the Wistar-Kyoto parent to the hypertensive state of the spontaneously hypertensive parent in the borderline hypertensive rat was accompanied by a similar transition of the renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress. Borderline hypertensive rats fed a 1% NaCl diet remained normotensive and exhibited renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress that were similar to those of their Wistar-Kyoto parent. Borderline hypertensive rats fed an 8% NaCl diet developed hypertension and exhibited responses that were similar to those of their spontaneously hypertensive parent. Thus, the dietary NaCl intake-induced transition from the normotensive state of the Wistar-Kyoto parent to the hypertensive state of the spontaneously hypertensive parent in the borderline hypertensive rat was accompanied by a similar transition of the renal sympathetic nerve activity and excretory responses to volume expansion and environmental stress. The results suggest that increased dietary NaCl intake is able to induce or unmask the capabilities for these responses, which are genetically conveyed to the borderline hypertensive rat by the spontaneously hypertensive rat parent in latent forms.

Animals↗

PubMed1991

Role of anteroventral third ventricle and vasopressin in renal response to stress in borderline hypertensive rats.

The borderline hypertensive rat is the first filial offspring of the spontaneously hypertensive rat and the Wistar-Kyoto rat. In response to acute environmental stress (air jet), the borderline hypertensive rat exhibits a diuretic response, whereas the parental strains exhibit an antidiuretic response (spontaneously hypertensive rat) or no change in urine flow rate (Wistar-Kyoto rat). This study sought to investigate the role of the periventricular tissue surrounding the anteroventral third ventricle and vasopressin release in the diuretic response of the borderline hypertensive rat to acute environmental stress. Sixteen-week-old borderline hypertensive rats who had consumed a 1% NaCl diet for 10-12 weeks were given either electrolytic lesions of the anteroventral portion of the third ventricle or sham lesions. When exposed to acute environmental stress 4 weeks later, the increase in volume of dilute urine seen in the sham-lesion rats was not observed in the lesion rats. Plasma vasopressin concentration was decreased by acute environmental stress in the sham-lesion rats (15.2 +/- 4.0 to 10.9 +/- 1.7 pg/ml, p less than 0.05) but was unchanged in the lesion rats (12.3 +/- 2.0 to 13.4 +/- 4.0 pg/ml). In a separate group of intact borderline hypertensive rats, a constant intravenous infusion of vasopressin prevented the diuretic response to acute environmental stress. The results suggest that acute environmental stress produces a diuresis in the borderline hypertensive rats via a decrease in plasma vasopressin concentration that is dependent on the integrity of the periventricular tissue of the anteroventral portion of the third ventricle.

Animals↗

PubMed1990

Effects of opioid peptides on neural control of renal function in spontaneously hypertensive rats.

The aims of the present study were to examine the effects of opioid receptor agonists and antagonists on the renal vascular (renal blood flow) and tubular (urinary sodium excretion) responses to renal nerve stimulation and norepinephrine in anesthetized spontaneously hypertensive rats (SHR). Graded frequency renal nerve stimulation (0.5-4.0 Hz) and doses of norepinephrine (10-80 ng/kg) produced frequency and dose-dependent decreases in renal blood flow. The renal vasoconstrictor responses were not altered by intravenous infusion of the opioid receptor agonists methionine enkephalin (mu and delta, 75 micrograms/kg/min) or U-50488H (kappa, 20 micrograms/kg/min) or administration of the opioid receptor antagonist naloxone (1 mg/kg i.v.). The antinatriuretic response to low frequency (less than 1.0 Hz) electrical renal nerve stimulation was prevented by naloxone but not affected by methionine enkephalin administration without changes in glomerular filtration rate or effective renal plasma flow. These studies suggest that endogenous opioid receptor mechanisms are involved in the increased renal tubular sodium reabsorption response to low frequency renal nerve stimulation but not in the renal vasoconstrictor response to either renal nerve stimulation or norepinephrine. This might occur by facilitation of the renal nerve terminal release, the direct renal tubular action, or both, of norepinephrine to influence renal tubular sodium reabsorption.

Animals↗

PubMed1989

Opioids in the systemic hemodynamic and renal responses to stress in spontaneously hypertensive rats.

Endogenous opioid peptides have been implicated in the regulation of cardiovascular and renal function. We tested this hypothesis by examining whether the opioid antagonist naloxone alters the cardiovascular or renal responses produced by environmental stress (air stress) in conscious spontaneously hypertensive rats (SHR). Before naloxone administration, air stress produced significant increases in heart rate, mean arterial pressure, and renal sympathetic nerve activity, and it caused a decrease in urinary sodium excretion. After intravenous and intracerebroventricular administration of naloxone, the air stress-induced pressor and antinatriuretic responses were inhibited. Subsequent studies with a different opioid antagonist, the quaternary compound naltrexone methylbromide, also showed inhibition of the air stress-induced pressor and antinatriuretic responses and demonstrated opioid receptor specificity of this inhibition. Furthermore, since only intracerebroventricular and not intravenous administration of naltrexone methylbromide inhibited the pressor and antinatriuretic responses to air stress, a central nervous system site of action was established. The opioid antagonists caused inhibition of the pressor and antinatriuretic responses to air stress without affecting the air stress-induced increase in renal sympathetic nerve activity. Our investigations indicate that central endogenous opioid peptides contribute to the pressor and antinatriuretic responses that occur in conscious SHR during acute environmental stress.

Animals↗

PubMed1989

Role of renal nerves in excretory responses to administration of kappa agonists in conscious spontaneously hypertensive rats.

The present study examined whether the renal sympathetic nerves contribute to the renal excretory responses produced by kappa opioid receptor agonist administration in conscious spontaneously hypertensive rats (SHR). Intravenous infusion of the kappa opioid receptor agonists, ketocyclazocine (KC) and U-50488H, produced increases in urine flow rate. KC and U-50488H infusion also resulted in a marked and sustained antinatriuresis which was promptly reversed by low-dose naloxone (50 micrograms/kg i.v.), thus suggesting an opioid receptor-mediated action of both agonists. Although these kappa agonists did not produce changes in glomerular filtration rate or renal plasma flow, efferent renal sympathetic nerve activity increased with the same time course as the antinatriuretic response. To investigate whether the decrease in urinary sodium excretion was mediated via the increase in efferent renal sympathetic nerve activity, experiments were repeated in SHR with prior bilateral renal denervation. These studies demonstrated that similar renal excretory responses (diuresis and a naloxone reversible antiinatriuresis occurred during infusion of KC and U-50488H in renal denervated as were seen in intact SHR. These studies indicate that the renal excretory responses to the kappa opioid agonists KC and U-50488H are not mediated through changes in renal hemodynamics or via a pathway requiring intact renal innervation. Because an antinatriuretic response was observed in renal denervated SHR, this suggests that kappa opioid receptor agonists may influence the renal tubular reabsorption of sodium by additional naloxone-sensitive mechanisms independent of intact renal innervation.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1989

Role of renal nerves in excretory responses to exogenous and endogenous opioid peptides.

The present study was designed to investigate opioid peptide-mediated changes in renal function in conscious Sprague-Dawley rats after administration of the native opioid agonist methionine enkephalin (ME), its synthetic analog D-Ala2-methionine enkephalinamide (DALA) and the opioid antagonist naloxone. Intravenous infusion of DALA (25 micrograms/kg/min) and ME (75 micrograms/kg/min) produced no changes in mean arterial pressure, heart rate, glomerular filtration rate or effective renal plasma flow in rats with intact or bilaterally denervated kidneys. In contrast, i.v. infusion of these opioid agonists produced differing effects on the renal excretion of water and sodium; DALA produced an increase in urinary flow rate and sodium excretion and ME produced a decrease in these parameters. Changes in renal sympathetic nerve activity were not involved in producing these effects as supported by measurements of renal sympathetic nerve activity and the finding that prior bilateral renal denervation did not alter the renal responses to either agonist. The renal excretory responses to both DALA and ME infusion were prevented by pretreatment with the opioid receptor antagonist naloxone, thus suggesting an opioid receptor-mediated effect of both agonists. Intravenous bolus injections of naloxone alone produced a dose-dependent diuresis and natriuresis without producing changes in systemic or renal hemodynamics or renal sympathetic nerve activity. These studies, therefore, provide evidence that the administration of opioid receptor agonists and antagonists produce changes in the renal excretion of water and sodium via an action on renal tubular reabsorptive mechanisms which are independent of changes in systemic or renal hemodynamics or renal sympathetic nerve activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗