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R K Handa

Publications and source records attributed to R K Handa.

29 records · Page 2Linked to original sources
PubMed1991

Vasorelaxant effect of C16-PAF and C18-PAF on renal blood flow and systemic blood pressure in the anesthetized rat.

The renal vasoactive and systemic hypotensive effects of platelet activating factor (C16:0-PAF and C18:1-PAF) were examined in anesthetized male Wistar rats. Bolus injections of C16-PAF (0.5-25 ng/kg) and C18-PAF (2.5-200 ng/kg) into the arterial circulation of the kidney produced increases in renal blood flow (6-15%) before causing dose-dependent systemic hypotension (2-64 mmHg). The dose-response curves for renal blood flow and systemic blood pressure generated by intrarenal C18-PAF administration were approximately 7 fold to the right of the dose-response curves generated by C16-DPAF. Intrarenal injections of vehicle or the biologically inactive enantiomer C16-DPAF (25-200 ng/kg) did not affect renal blood flow or systemic blood pressure. These results suggest that C16:0-PAF is a more potent renal vasodilator and hypotensive lipid than C18:1-PAF.

Anesthesia↗
PubMed1991

Selective inhibition of vasoconstrictor responses by platelet-activating factor in rat kidney.

We examined the effect of platelet-activating factor (PAF) on renal vascular reactivity in the pentobarbital sodium-anesthetized male Wistar rat. Intrarenal infusion of C16-PAF at hypotensive (2.5 ng.min-1.kg-1) or nonhypotensive (0.5 ng.min-1.kg-1) doses caused renal vasodilation and dose dependently antagonized the renal vasoconstrictor responses of intrarenal boluses of angiotensin II (ANG II) greater than norepinephrine (NE) greater than vasopressin (AVP). PAF infusion at the high dose did not alter non-receptor-mediated renal vasoconstriction induced by intrarenal KCl injection. The inhibitory effect of PAF on agonist-induced renal vasoconstriction was accentuated by eicosanoid synthesis inhibition (indomethacin or dexamethasone), unaffected by dopamine-receptor blockade (haloperidol) but was totally abolished by PAF receptor antagonism (L-659,989). In contrast, intrarenal infusion of a calcium channel antagonist (nimodipine) or an intracellular calcium channel antagonist (TMB-8) equally inhibited the renal vasoconstrictor responses of ANG II, NE, and AVP. Thus PAF can cause renal vasodilation in the rat kidney and dose-dependently antagonizes the renal vasoconstrictor responses of ANG II greater than NE greater than AVP. The inhibitory effect of PAF on renal vasoconstrictor responses is mediated by PAF receptors and does not appear to be due to a nonspecific membrane effect, reduction in calcium mobilization, or the release of vasodilatory eicosanoids or dopamine.

Animals↗
PubMed1990

Platelet-activating factor is a renal vasodilator in the anesthetized rat.

In view of the potent vasoactive properties of platelet-activating factor (PAF), we investigated the renal hemodynamic effects of this lipid. C16-PAF (0.5-10 ng/kg) given as a bolus into the renal arterial circulation of pentobarbital sodium-anesthetized male Wistar rats produced a dose-dependent increase in renal blood flow (6-15%), before causing systemic hypotension. The PAF-induced renal vasodilation and systemic hypotension was independent of renal innervation, unaltered by eicosanoid synthesis inhibition with indomethacin or dexamethasone, unchanged by the nonselective dopamine-receptor antagonist haloperidol, but was abolished by the PAF-receptor antagonist, L-659,989. Non-hypotensive intrarenal PAF infusion at 0.5 ng.min-1.kg-1 caused an increase in renal blood flow. Thus PAF can cause renal vasodilation in the rat kidney that is PAF-receptor mediated and does not involve the sympathetic nervous system or the release of vasodilatory arachidonic acid metabolites or dopamine.

Anesthesia↗
PubMed1990

Glucocorticoids and control of glomerular filtration rate.

Glucocorticoids given acutely or chronically at physiological/pharmacological doses increase GFR in both experimental animals and humans. Glomerular micropuncture studies have shown that in the normal rat kidney, glucocorticoids vasodilate both the preglomerular and efferent resistances and result in an increase in glomerular plasma flow, which is the sole factor responsible for the increase in GFR. However, the mechanism(s) initiating these alterations in the glomerular microcirculation remain obscure. The glucocorticoid-induced increase in GFR does not appear to be due to volume expansion or alteration in tubulo-glomerular feedback activity. Chronic glucocorticoid administration has been shown to increase renal prostaglandin synthesis in some but not all species; however, a link between increased prostaglandin production and glucocorticoid-induced increase in GFR has not been established. A number of studies have examined glucocorticoid-induced alterations in renal vascular reactivity to vasoconstrictor agonists and the data have been conflicting. The suggestion that glucocorticoid-stimulated ANP production evokes the increase in GFR is unlikely to be correct based on substantial differences in the glomerular hemodynamic changes seen with ANP or glucocorticoids. An interesting proposal that appears well worth exploring is that glucocorticoids may increase GFR through their effects on catabolism of proteins to increase production of amino acids. Amino acid infusion markedly elevates GFR and has a similar glomerular hemodynamic profile as that of glucocorticoids. By virtue of their action to increase GFR, glucocorticoids increase the rate of electrolyte and water delivery into the nephron. Therefore, glucocorticoid-induced alterations in electrolyte and water excretion may be secondary to an elevation in GFR, in addition to direct actions of glucocorticoids on the tubule. Also, by determining the hemodynamic state of the kidney, and hence, rate of fluid delivery through the nephron, glucocorticoids may influence the sensitivity of the nephron to regulatory influences. Glucocorticoids have their most profound effect (especially clinically) by modifying the immunological or cellular mechanisms responsible for glomerular injury. Less important is their ability to increase GFR. In view of some evidence that suggests increasing glomerular pressure accelerates the progression of established renal disease, some might speculate that glucocorticoids actually increase glomerular damage under certain conditions.

Animals↗
PubMed1988

A study of the renal responses in the rat to electrical stimulation of the afferent nerves of the brachial plexus.

Brachial nerve stimulation at 3 Hz in sodium pentobarbitone-anaesthetized rats, with constant renal arterial pressure, increased systemic blood pressure, did not alter glomerular filtration rate but reduced renal blood flow, absolute and fractional sodium excretions and urine flow. In renally denervated animals, stimulation caused similar changes in blood pressure and renal haemodynamics but significantly smaller reductions in sodium and water excretions. Brachial nerve stimulation at 30 Hz caused changes in blood pressure and renal function identical to those obtained with low-frequency stimulation but these responses were not modified by renal denervation. The results show that renal nerves are necessary to promote sodium and water reabsorption in response to low- but not high-frequency stimulation of the brachial nerves in the rat.

Afferent Pathways↗
PubMed1987

The role of angiotensin II in the renal responses to somatic nerve stimulation in the rat.

1. Electrical stimulation of the brachial nerves at 3 Hz (15 V, 0.2 ms), in sodium pentobarbitone-anaesthetized rats whose renal arterial pressure was held constant, elicited a 26% increase in systemic blood pressure, a 15% rise in heart rate, an 11% reduction in renal blood flow, did not alter glomerular filtration rate and significantly reduced absolute and fractional sodium excretions and urine flow by 44, 49 and 31%, respectively. 2. In a separate group of rats, brachial nerve stimulation at 3 Hz increased plasma renin activity approximately 2-fold, while in animals in which the brachial nerves were not stimulated plasma renin activity did not change. 3. Following inhibition of the renin-angiotensin system with captopril or sar-1-ile-8-angiotensin II, brachial nerve stimulation resulted in similar increases in systemic blood pressure and heart rate as in the animals with an intact renin-angiotensin system but, in captopril-infused rats, did not change renal haemodynamics or urine flow while absolute and fractional sodium excretions were reduced by 20 and 25%, respectively. In sar-1-ile-8-angiotensin II-infused animals, similar nerve stimulation decreased renal blood flow by 12%, glomerular filtration rate by 7% and absolute and fractional sodium excretions and urine flow by 25, 18 and 18%, respectively. These decreases in sodium and water output were significantly smaller than those observed in animals with an intact renin-angiotensin system. 4. Stimulation of the brachial nerves increased post-ganglionic efferent renal nerve activity by 20% and the magnitude of this response was unaffected following inhibition of the renin-angiotensin system. 5. The results show that low rates of brachial nerve stimulation in the rat can increase efferent renal nerve activity and result in an antinatriuresis and antidiuresis which is dependent on the presence of angiotensin II, and appears to be due to an action of angiotensin II at the level of the kidney.

1-Sarcosine-8-Isoleucine Angiotensin II↗
PubMed1987

Age-related changes in adrenergic vasoconstrictor responses of the rat hindlimb.

Vascular adrenergic responses were examined in the hindlimb perfused with blood at constant flow using pentobarbital-anesthetized male Fischer 344 rats aged 6, 12, 20, and 24 mo. The increase in hindlimb perfusion pressure to lumbar sympathetic nerve stimulation was significantly smaller in 20- and 24-mo-old rats than in younger animals, whereas vasoconstrictor responses to intraarterial administration of norepinephrine, L-phenylephrine, and methoxamine were reduced only in the 24-mo-old animals. Thus neurogenic vasoconstriction in the hindlimb is reduced at 20 mo of age, whereas there is a more generalized postjunctional loss of adrenergic responsiveness at 24 mo. In the presence of the beta-adrenoceptor antagonist, propranolol, vasoconstrictor responses to exogenous norepinephrine did not differ when 12- and 20-mo-old animals were compared. Furthermore, in the presence of propranolol the nerve-mediated rise in hindlimb perfusion pressure also did not differ in 12- and 20-mo-old rats. Blockade of neuronal norepinephrine uptake with cocaine produced a greater potentiation of vasoconstrictor responses to both nerve stimulation and exogenous norepinephrine in the older rats. Therefore, the reduced nerve-mediated vasoconstriction in 20-mo-old rats may be due to neuronal activation of beta-adrenoceptors as well as enhanced neuronal norepinephrine reuptake.

Adrenergic Fibers↗
PubMed1985

Interaction of the renin-angiotensin system and the renal nerves in the regulation of rat kidney function.

Stimulation of the renal sympathetic nerves in pentobarbitone anaesthetized rats achieved a 13% reduction in renal blood flow, did not change glomerular filtration rate, but reduced urine flow by 37%, absolute sodium excretion by 37%, and fractional sodium excretion by 34%. Following inhibition of converting enzyme with captopril (0.38 mmol kg-1 h-1), similar nerve stimulation reduced both renal blood flow and glomerular filtration rate by 16%, and although urine flow and absolute sodium excretion fell by 32 and 31%, respectively, the 18% fall in fractional sodium excretion was significantly less than that observed in the absence of captopril. Renal nerve stimulation at low levels, which did not change either renal blood flow or glomerular filtration rate, reduced urine flow, and absolute and fractional sodium excretions by 25, 26 and 23%, respectively. In animals receiving captopril at 0.38 mmol kg-1 h-1, low-level nerve stimulation caused small increases in glomerular filtration rate of 7% and urine flow of 12%, but did not change either absolute or fractional sodium excretions. At one-fifth the dose of captopril (0.076 mmol kg-1 h-1), low-level nerve stimulation did not change renal haemodynamics but decreased urine flow, and absolute and fractional sodium excretions by 10, 10 and 8%, respectively. These results showed that angiotensin II production was necessary for regulation of glomerular filtration rate in the face of modest neurally induced reductions in renal blood flow and was compatible with an intra-renal site of action of angiotensin II preferentially at the efferent arteriole. They also demonstrated that in the rat the action of the renal nerves to decrease sodium excretion was dependent on angiotensin II.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

Influence of age on norepinephrine content in arteries and veins of Fischer 344 rats.

The norepinephrine content of blood vessels in male Fischer 344 rats aged 6, 12, 20 and 27 months was measured by electrochemical detection after alumina extraction and high-performance liquid chromatography separation. With the exception of the superior mesenteric artery which showed no age-related changes in norepinephrine content and the caudal artery which showed an increase from 12 to 27 months of age, all other arteries examined (renal, femoral, saphenous, superficial epigastric, and popliteal) showed a significant decline in norepinephrine content with advancing age. In contrast, the content of norepinephrine in the renal, femoral, saphenous and superior mesenteric veins remained constant at all ages. Since norepinephrine in the blood vessel wall is predominantly localized to sympathetic nerve endings, the decline in norepinephrine content in most arteries of old rats may reflect a selective decrease in the density of sympathetic neurons or alternatively an age-related alteration in the metabolic properties of these sympathetic nerve endings.

Aging↗
PubMedDate not supplied

Vasopressin induces dopamine release and cyclic AMP efflux from the brain of water-deprived rats: inhibitory effect of vasopressin V2 receptor-mediated phosphorylation.

The neurohypophyseal hormone vasopressin (AVP) is widely distributed throughout the central nervous system. It acts as an excitatory transmitter in the CNS and plays an important physiological role in water and electrolyte homeostasis. However, water deprivation has been shown to induce changes in the levels of monoamines, but there is little knowledge about the influence of AVP on monoamine levels after water deprivation. In this study, we investigated the effect of AVP and its receptor antagonists on alterations in dopamine (DA) release and cyclic adenosine 3',5' monophosphate (cAMP) efflux from rat brain slices following water deprivation. Striatal brain slices (500 microm thick) were incubated in a medium with or without AVP (0. 1-1.0 microM) for 30 min. After 2 h of washout in normal medium, high KCl (40 mM)-evoked DA release and cAMP efflux from the rat brain slices were examined. In the brain slices of euhydrated animals, treatment with AVP slightly altered DA release and cAMP efflux from the brain. This increase in DA release and cAMP efflux was not significantly affected by the addition of a calcium/calmodulin-dependent protein phosphatase, calcineurin (20 microM), to the incubation medium or either by a V1 or V2 AVP receptor antagonist. In contrast, AVP significantly increased the DA release and enhanced the cAMP efflux from the brain slices of water-deprived animals. The AVP-induced increase of brain response in the water-deprived animals was significantly attenuated by a V2 receptor antagonist, partially by calcineurin, but not by a V1 receptor antagonist. The present results suggest that AVP may play a role in water-deprivation-induced DA release and cAMP efflux, which is possibly mediated through the activation of the V2 receptor. The V2 receptor action is attenuated by calcium/calmodulin-dependent dephosphorlyation of some cellular proteins critical for signal transduction.

Animals↗