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J C Pelayo

Publications and source records attributed to J C Pelayo.

26 records · Page 2Linked to original sources

Angiotensin II in adrenergic-induced alterations in glomerular hemodynamics.

UNLABELLED: Micropuncture analysis of glomerular ultrafiltration (SNGFR) was conducted in Munich-Wistar rats to assess the functional responses to moderate-frequency (3-Hz) renal nerve stimulation. Angiotensin II inhibition (ANG II-inhib) was produced by the intravenous administration of [Sar1, Ala8] angiotensin II or MK 421 to investigate whether it modulates the effects of renal nerve stimulation. Micropuncture measurements were obtained before and during renal nerve stimulation. Renal nerve stimulation decreased SNGFR approximately 25% (from 49.9 +/- 2.3 to 38.0 +/- 1.4 nl X min-1 X g kidney wt-1), the result of decreased glomerular capillary hydrostatic pressure gradient and nephron plasma flow. These decreases were due to increased afferent (approximately 43%) and efferent (approximately 30%) arteriolar resistances, since the glomerular ultrafiltration coefficient remained unaffected. The effects of renal nerve stimulation during ANG II-inhib were less in magnitude than in renal nerve stimulation alone: SNGFR decreased from 48.0 +/- 1.5 to 44.8 +/- 2.0 nl X min-1 X g kidney wt-1 after renal nerve stimulation. The net renal production of norepinephrine was augmented by renal nerve stimulation but it was not influenced by ANG II-inhib. IN CONCLUSION: renal nerve stimulation can regulate glomerular ultrafiltration by altering vascular resistances, and angiotensin II appears to be a critical factor for the full functional expression of renal nerve stimulation at the glomerulus.

Angiotensin II↗

Renal denervation in the rat: analysis of glomerular and proximal tubular function.

We examined 1) the potential modifications in both single nephron filtration rate (SNGFR) and the determinants of glomerular ultrafiltration, and 2) the alterations in peritubular capillary (PTC) "physical factors" that may contribute to changes in proximal tubular reabsorption (APR) after acute renal denervation (DNx). Micropuncture measurements were obtained in euvolemic Munich-Wistar rats with DNx or sham operation (sham). The content of norepinephrine in renal tissue homogenates was markedly reduced in DNx kidneys compared with sham kidneys (P less than 0.001). Mean arterial blood pressure, hematocrit, whole kidney GFR, and urinary flow rate were not different between the sham and DNx groups. Absolute urinary sodium excretion was 3 times greater in the DNx than in the sham group (P less than 0.01). SNGFR and its determinants were not statistically different in the two experimental conditions. APR was significantly reduced by approximately 25% in DNx (P less than 0.02). This reduction in APR was not accompanied by significant directional changes in peritubular capillary and renal interstitial pressures and the passive driving forces acting across the PTC-proximal tubular epithelium. These data demonstrate that elimination of renal innervation does not alter SNGFR or its determinants and suggest that the effect of denervation on APR is a primary epithelial event that occurs independent of changes in renal interstitial pressure and peritubular oncotic and hydrostatic pressures.

Absorption↗

Effects of dopamine blockade on renal sodium excretion.

The renal responses to a specific dopamine antagonist (cis-flupentixol) and its stereoisomer (trans-flupentixol), a weak dopamine antagonist, were examined during hydropenia and Ringer loading in anesthetized rats. During hydropenia glomerular filtration (GFR), absolute (UNaV), and fractional (FENa) sodium excretion rates were similar as were single-nephron filtration (SNGFR) and proximal tubular flow rate (VTF). After Ringer loading GFR, UNaV, and FENa increased in all groups, but the increments were less in the cis-flupentixol than in the control or trans-flupentixol group. SNGFR and VTF increased similarly in all groups. In another series of experiments Ringer loading was performed prior to drug administration. Perfusion pressure (PP) was decreased in trans-flupentixol rats by aortic constriction to control for cis-flupentixol-induced reduction in PP. UNAV and FENa were lower in the cis-flupentixol- than trans-flupentixol-treated rats at comparable PP and GFR. In conclusion, dopamine blockade attenuated the natriuresis of Ringer loading; the mechanism is uncertain but may be related to a tubular effect at a site beyond the proximal convoluted tubule and/or in deeper nephrons.

Animals↗

Alpha-adrenoceptors in the developing kidney.

The maturation of renal alpha-adrenoceptors was investigated in dogs. Alpha-adrenoceptors were characterized by radioligand binding using the alpha-1-adrenergic antagonist, [3H]-WB-4101. In renal plasma membranes obtained from the outer cortex of neonates, the binding of the ligand was rapid, reversible, of high affinity, saturable, and stereoselective. The competition studies with adrenergic agonists and antagonists were indicative of alpha-receptors. In puppies less than 1-w-old, the binding affinity of [3H]-WB-4101 (Kd = 0.638 +/- 0.17 nM) was greater than 3-5 week-old puppies (Kd 1.573 +/- 0.315 nm); (P less than 0.05), but receptor number was similar (63.75 +/- 19.1 versus 79.10 +/- 5.99 fmole/mg protein). No consistent specific binding could be demonstrated in plasma membranes obtained from inner cortex of medulla. In the adult dog, no consistent specific binding could be demonstrated for plasma membranes obtained from any region of the kidney. These studies indicate that during maturation there is a decrease in alpha-adrenoceptor density and affinity in membranes from the outer cortex of the kidney.

Adrenergic alpha-Antagonists↗

The influence of age on acute renal toxicity of uranyl nitrate in the dog.

The influence of age upon uranyl nitrate (UN) induced acute renal failure (ARF) was evaluated in 30 canine puppies 1-2 wk and 3-5 wk old. Renal function and morphologic studies were performed 2 h (initiation phase) and 24 h (maintenance phase) after UN administration. Age-matched controls received vehicle alone. Administration of UN to 1-2-wk-old puppies produced no changes in whole kidney glomerular filtration rate (GFR), despite a significant reduction in renal plasma flow (RPF) (P less than 0.01). In contrast, during the maintenance phase, GFR was 60% lower than in the control group (P less than 0.02) whereas values for RPF were nearly identical to control values. In 3-5-wk-old puppies the magnitude of response to the heavy metal was much greater and GFR was nearly completely suppressed during the maintenance phase. This major alteration of GFR was independent of changes in RPF, because RPF remained similar to control values. Morphologic alterations consistent with the nephrotoxic effects of UN were observed in the proximal tubules of the most differentiated nephrons. These age-related morphologic alterations correlated well with the functional response (GFR) observed after UN administration, i.e., a proportionately greater degree of both morphologic and functional alterations followed the administration of the heavy metal in the oldest group of puppies.

Acute Kidney Injury↗

In vivo actions of angiotensin II on glomerular function.

Investigations in which a variety of experimental approaches were used, i.e., micropuncture techniques, analysis of intrarenal hormonal receptor, and electron microscopic analysis of renal morphology, have substantiated a major role for angiotensin II (AII) within the kidney in the regulation of vascular resistances, glomerular function, and even tubular reabsorption. It is also clear that AII exerts a significant influence on glomerular hemodynamics in a variety of altered physiological and pathophysiological states. Recent studies suggest a rather complex interaction between AII and hormonal and adrenergic effects at the glomerular level. AII may also play an important functional role in the pathogenesis of certain forms of acute renal failure. The specific mechanism whereby AII decreases the glomerular ultrafiltration coefficient, however, remains to be fully elucidated. Although in vitro and in vivo studies have suggested that the glomerular effects of AII may be associated with contraction of glomerular mesangial cells, recent in vivo quantitative evaluation has suggested that a uniform vasoconstriction of glomerular capillaries with proportional reductions in glomerular surface area is probably not the sole mechanism for the AII-induced reductions in glomerular ultrafiltration coefficient.

Angiotensin II↗

Cyclic nucleotide response to stimulation in isolated glomeruli from dog kidney.

The effects of biogenic amines on cyclic 3',5'-adenosine monophosphate (cAMP) and on cyclic 3',5'-guanosine monophosphate (cGMP) were studied in isolated glomeruli from dog kidneys. Of the agents tested, histamine produced the greatest increase in cyclic nucleotide activity. Isoproterenol, dopamine, epinephrine and norepinephrine also produced increases in cAMP and/or cGMP activity but of lesser magnitude. Propranolol decreased cyclic nucleotide levels. Glomeruli isolated from the outer cortex showed greater responses to stimulation than glomeruli from the inner cortex.

Animals↗