Biomedical subjects

D R Kapusta

Publications and source records attributed to D R Kapusta.

29 records · Page 2Linked to original sources

PubMed1995

Hydroxocobalamin (vitamin B12a) prevents and reverses endotoxin-induced hypotension and mortality in rodents: role of nitric oxide.

The cobalt atom of hydroxocobalamin (OHC) binds cyanide and nitric oxide (NO) and OHC attenuates vascular responses to NO in vitro. NO mediates the hypotension of endotoxemia. Thus, we tested the postulate that OHC may attenuate the acute phase hypotension and toxicity associated with administration of Escherichia coli endotoxin (LPS). Rats were given OHC (20 mg/kg i.v.) or phosphate-buffered saline (PBS, 1 ml/kg i.v.) 30 min before or 15 min after giving LPS (0.8 mg/kg i.v.). Administration of OHC to PBS-treated control rats did not affect mean arterial pressure (MAP), heart rate or the plasma or urine content of the reactive nitrogen intermediates nitrate and nitrite (RNI). LPS decreased MAP by 50 mm Hg in PBS-treated rats and increased the plasma and urinary content of RNI. Administration of OHC to PBS-treated rats did not affect MAP or RNI. However, treatment with OHC before or after giving LPS attenuated LPS-induced hypotension and increases in plasma RNI and enhanced LPS-induced urinary excretion of RNI. OHC (20 mg/kg i.p.) or cyanocobalamin (10 mg/kg i.p.) given to Swiss-Webster mice 30 min before giving LPS (16 mg/kg i.p.) decreased the 24-hr mortality of LPS from 80 to 50% and the 36- and 96-hr mortality from 100 to 60% (OHC) or 70% (cyanocobalamin). Urine obtained from conscious rats given LPS (5 mg/kg i.p.) and OHC (20 mg/kg i.p.) exhibited a UV-visible absorbance spectrum with absorbance peaks characteristic of that formed after coincubation of NO and OHC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Central mu opioid receptor-mediated changes in renal function in conscious rats.

Studies were performed in conscious Sprague-Dawley rats to determine whether the renal sympathetic nerves contribute to the renal excretory responses produced by central mu opioid agonist administration. Intracerebroventricular, but not i.v. injection of the selective mu opioid agonist dermorphin (0.1 nmol/kg), produced an increase in urine flow rate and a sustained decrease in urine sodium excretion. These renal excretory responses were completely prevented by pretreatment with the selective mu opioid antagonist, beta-funaltrexamine (20 micrograms, i.c.v.). Central dermorphin administration did not alter glomerular filtration rate or effective renal plasma flow. In contrast, efferent renal sympathetic nerve activity increased over the same time frame as the reduction in urinary sodium excretion. To investigate whether the dermorphin-induced antinatriuretic response was mediated via the increase in renal sympathetic nerve activity, experiments were repeated in Sprague-Dawley rats that had undergone chronic bilateral renal denervation. In renal denervated rats, i.c.v. dermorphin produced similar diuretic and antinatriuretic responses as were seen in rats with an intact renal innervation. Together, these studies indicate that the changes in urine flow rate and urinary sodium excretion produced by i.c.v. dermorphin were not mediated via central induced changes in renal hemodynamics or sympathetic outflow to the kidneys. Because an antinatriuretic response occurred in renal denervated animals, this suggests that central mu opioid receptor agonists may exert an influence on tubular reabsorption of sodium via mu opioid receptor-mediated mechanisms independent of intact renal innervation.

Analgesics, Opioid↗

PubMed1993

Central kappa opioid receptor-evoked changes in renal function in conscious rats: participation of renal nerves.

The present investigations examined the cardiovascular and renal responses produced by central nervous system stimulation of kappa opioid receptors by the selective kappa opioid receptor agonist, U-50488H, in conscious Sprague-Dawley rats. Administration of U-50488H (1 microgram total) into the lateral cerebroventricle produced a profound diuretic and antinatriuretic response. In addition, concurrent with the decrease in urinary sodium excretion, i.c.v. U-50488H elicited an increase in renal sympathetic nerve activity. The increases in urine flow rate and renal sympathetic nerve activity and the decrease in urinary sodium excretion produced by U-50488H were completely prevented in rats that had undergone pretreatment with the selective kappa opioid receptor antagonist, nor-binaltorphimine. In contrast, in animals that had undergone irreversible mu opioid receptor blockade with the selective mu opioid receptor antagonist, beta-funaltrexamine, central U-50488H administration elicited similar diuretic and antinatriuretic responses as observed in intact naive animals. In further studies, the antinatriuretic response produced by i.c.v. U-50488H was completely abolished in rats that had undergone chronic bilateral renal denervation, a technique used to remove the influence of the renal sympathetic nerves. Glomerular filtration rates and effective renal plasma flows were not altered by i.c.v. administration of U-50488H in intact or renal denervated animals. Together, these studies provide evidence for the role of central kappa opioid receptor mechanisms in the regulation of urinary sodium and water excretion. Moreover, these studies indicate that the changes in renal sodium handling produced by central kappa opioid agonists result from an action of these compounds to modulate sympathetic neural outflow to the kidneys.

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

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↗

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

Selective central alpha-2 adrenoceptor control of regional haemodynamic responses to air jet stress in conscious spontaneously hypertensive rats.

The role of central nervous system alpha 2-adrenoceptors in the regulation of peripheral sympathetic outflow to regional vascular resistance beds during environmental stress was examined in conscious chronically instrumented spontaneously hypertensive rats (SHR). SHR were instrumented with pulsed Doppler flow probes on the renal and mesenteric arteries and the lower abdominal aorta. The mean arterial pressure (MAP), heart rate and regional vascular resistance responses to air jet stress were determined before and after cumulative administration of the alpha 2-adrenoceptor agonist, guanabenz, into the lateral cerebral ventricle in doses of 5 and 25 micrograms. Compared with intracerebroventricular (i.c.v.) administration of isotonic saline vehicle which did not affect baseline systemic and regional haemodynamic measurements, guanabenz produced significant decreases in baseline MAP and heart rate but did not affect regional vascular resistances. During air jet stress, the characteristic pattern of the classic defense reaction with an increase in MAP, heart rate, renal and mesenteric vascular resistances and a decrease in hindquarters vascular resistance was observed and was not affected by i.c.v. administration of isotonic saline vehicle. Guanabenz did not affect the MAP, heart rate or renal vascular resistance responses to air jet stress. The air jet stress-induced increase in mesenteric vascular resistance was reduced by 25 micrograms guanabenz. The air jet stress-induced decrease in hindquarters vascular resistance was converted to an increase by 25 micrograms guanabenz. These results demonstrate that the regulation of environmental stress-stimulated sympathetic neural outflow to different vascular beds may be independently controlled by central nervous system alpha 2-adrenoceptors.

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↗

PubMed1988

Effects of cocaine and nomifensine on canine renal venous norepinephrine and dopamine content during electrical stimulation of the renal nerves.

Dopamine has been suggested to play a role in the regulation of renal blood flow following its neuronal release from within the kidney. Skepticism remains, however, as to whether a vascular dopaminergic innervation plays a physiologic role in renal blood flow regulation. Thus, to investigate this possibility, we examined whether electrical stimulation of the renal nerves evokes an overflow of dopamine into renal venous blood that could be augmented by cocaine or nomifensine, two inhibitors of presynaptic uptake. To verify uptake inhibition, the stimulation-induced overflow of norepinephrine (NE) was also examined. The increases in renal venous NE content observed during 0.5 and 2.0 Hz renal nerve stimulation were significantly increased by administration of cocaine (2.5 and 5.0 mg/kg) and nomifensine (1 mg/kg). Renal nerve stimulation (0.5 and 2.0 Hz) did not significantly increase free renal venous or total dopamine sulfate content before or following administration of either cocaine or nomifensine. Renal venous minus arterial dopamine content indicated that a neuronal release of dopamine into renal venous blood could not be clearly demonstrated in the canine kidney. These results do not support the existence of an active dopaminergic innervation of the renal vasculature involved in the regulation of renal blood flow.

Animals↗

PubMed1988

Plasma dopamine in regulation of canine renal blood flow.

Studies were performed in pentobarbital-anesthetized dogs to determine whether circulating plasma dopamine (DA) is involved in renal blood flow (RBF) regulation. During graded reductions in renal perfusion pressure (RPP), total renal venous (RV) DA content significantly increased at RPPs below the autoregulatory range. The RBF response to decrements in RPP was also examined during control, infusion of DA (1.2 micrograms.kg(-1).min(-1)ia), and after DA receptor blockade by SCH 23390 (30 micrograms/kg iv). During DA infusion, autoregulation was still evident over the same RPPs, although at higher flow rates. At pressures below the autoregulatory range, RBF decreased linearly and the autoregulatory curve merged with control at 50 mmHg. After SCH 23390, autoregulation ceased at a higher RPP than during control, and RBF was significantly less than control rates at pressures of 80 mmHg and below. To elucidate reasons for this latter response, reductions in RPP were repeated before and after administration of both prazosin (0.1 mg/kg iv) and SCH 23390. The results indicated that RBF rates were not different from control at any RPP. Further, prazosin alone did not alter renal autoregulation but significantly increased RBF at RPP below the autoregulatory range. Thus these results indicate that dopamine does not participate in RBF control at pressures above the inflection point for the lowest limit of RBF autoregulation but may be released at lower RPP to act as a vasodilator agent to oppose alpha-adrenoceptor-mediated reductions in RBF. Moreover, tonic DA receptor activation may influence the setting of the lower limit of canine RBF autoregulation.

Animals↗