1. Angiotensin II was infused into the renal artery of intact kidneys of slightly volume expanded anaesthetized dogs at rates of 125, 250, 500, and 1000 pg/kg body weight per min, resulting in elevations of the calculated renal arterial plasma angiotensin II concentration of 16.9 (s.e.m. =2.1), 35.0 (s.e.m.=4.3), 73.3 (s.e.m.=8.8), and 159.8 (s.e.m.=20.4)pg/ml...

Angiotensin II↗

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Extracellular ATP increases cytosolic calcium in cultured rat renal arterial smooth muscle cells.

1. Experiments were conducted on cultured renal arterial smooth muscle cells to determine the ability of extracellular ATP to alter cytosolic calcium concentration and to determine the mechanisms by which this effect occurs. 2. ATP (100 mumol/L) caused the fluorescence ratio of fura-2 to increase from a control value of 1.06 +/- 0.05 to 2.06 +/- 0.13 (P < 0.01) before stabilizing at a sustained level of 1.35 +/- 0.04 (n = 8; P < 0.05). 3. Removal of extracellular calcium from the bathing medium resulted in an attenuation of the initial response to 100 mumol/L ATP with cell fluorescence increasing from 1.16 +/- 0.18 to 1.44 +/- 0.18 ratio units (n = 5). Furthermore, the initial increase in fluorescence ratio rapidly declined to 1.02 +/- 0.06, indicating that an influx of extracellular calcium is required to sustain the increase in fura-2 fluorescence. 4. Depletion of intracellular calcium pools with thapsigargin prevented the increase in fura-2 fluorescence evoked by ATP. 5. These data suggest that ATP-mediated increases in cytosolic calcium in cultured renal arterial smooth muscle cells involve calcium release from the thapsigargin-sensitive, intracellular pool in conjunction with calcium influx from the extracellular medium.

Adenosine Triphosphate↗

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Influence of intrarenally generated angiotensin II on renal hemodynamics and tubular reabsorption.

There is growing recognition that angiotensin II (ANG II) formed intrarenally exerts direct effects on renal hemodynamics and tubular reabsorption. In vivo micropuncture experiments performed in anesthetized rats have shown that peritubular capillary infusion of either ANG II or angiotensin I (ANG I), at rates that do not markedly influence baseline vascular resistance, can increase proximal tubular reabsorption rate and enhance the responsiveness of the tubuloglomerular feedback mechanism. With higher ANG II or ANG I infusion rates, pronounced preglomerular vasoconstriction occurs, resulting in reduced glomerular capillary pressure and single nephron glomerular filtration rate. The effects of peritubular capillary infusion of ANG I on glomerular function have been shown to be inhibited by the ANG II receptor antagonist, saralasin, indicating that the observed effects of ANG I on proximal tubular reabsorption and glomerular function are not due to direct effects of the decapeptide but are mediated by increases in the interstitial ANG II concentrations resulting from intrarenally generated ANG II. Interestingly, neither peritubular capillary infusion nor systemic administration of large doses of the angiotensin-converting enzyme (ACE) inhibitor, enalaprilat, elicited significant blockade of the single nephron hemodynamic responses to peritubular infusion of ANG I. These findings indicate that intrarenal conversion of ANG I to ANG II occurs, at least in part, at a site which is inaccessible to acutely administered ACE inhibitors, or that there is an alternative pathway for the intrarenal conversion of ANG I to ANG II that is not blocked by ACE inhibitors.

Absorption↗

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Glomerular and renal hemodynamics during converting enzyme inhibition (SQ20,881) in the dog.

It has been suggested that intrarenal levels of angiotensin II may preferentially control efferent arteriolar resistance or may influence the glomerular filtration coefficient (Kf). To examine these possibilities, micropuncture and clearance experiments were performed on nine anesthetized dogs evaluating renal and glomerular hemodynamics before and during the administration of an angiotensin converting enzyme inhibitor (SQ20,881). During the micropuncture measurements, renal arterial pressure was reduced to range of 85 to 90 mm Hg in order to maximize renin secretion and intrarenal formation of angiotensin II. Also, this procedure minimizes potential errors in the determination of single nephron glomerular filtration rate (SNGFR) and of glomerular pressure when estimated by techniques that require complete blockade of proximal tubule fluid flow. During the administration of SQ20,881, a converting enzyme inhibitor (CEI), renal blood flow increased significantly by 13%, but GFR was not altered. There were no significant alterations in SNGFR, proximal tubule pressure, peritubular capillary pressure or estimated glomerular pressure. By using the micropressure measurements in combination with the whole kidney hemodynamic data, it was estimated that afferent resistance was reduced 23%. Although significant decreases in efferent resistance could not be documented, there was a tendency for this variable to decrease also. Neither Kf nor effective filtration pressure were altered significantly by CEI. These results do not support the contention that intrarenal effects of angiotensin II are exerted predominantly on the efferent arteriolar resistance segments; rather, they suggest that angiotensin may exert a modest tonic effect on both pre- and postglomerular resistance elements in the anesthetized hydropenic dog.

Angiotensin II↗

PubMedDate not supplied

Impaired renal blood flow and cortical pressure autoregulation in contralateral kidneys of Goldblatt hypertensive rats.

Experiments were conducted on two-kidney, one clip renal vascular hypertensive rats to assess the ability of the kidney contralateral to renal vascular stenosis to autoregulate renal blood flow (RBF), glomerular filtration rate (GFR), and hydrostatic pressures in cortical structures during conditions of acutely reduced renal arterial blood pressure (BP). When observed at their respective, spontaneous BPs, RBF and GFR were not different in the contralateral kidneys of the hypertensive rats (n = 11) compared to normal animals (n = 7). However, the contralateral kidneys exhibited a significantly higher renal vascular resistance (RVR), 28.9 +/- 2.8 mm Hg . min/ml than the control animals, 23.1 +/- 1.5 mm Hg . min/ml. At spontaneous BP (169 +/- 5 mm Hg), urine flow, absolute and fractional sodium excretion, and absolute and fractional potassium excretion were all significantly greater in the contralateral kidneys of hypertensive rats than in kidneys of normal rats. Hydrostatic pressures in cortical structures were similar in the two groups. When BP was reduced acutely, the kidney contralateral to the renal artery stenosis achieved only small decreases in RVR that failed to allow RBF, GFR, or cortical pressures to be maintained. In contrast, normal rats efficiently autoregulated RBF and GFR. In addition, hydrostatic pressures in proximal tubules, distal tubules, and first order peritubular capillaries were maintained during reductions in BP to as low as 100 mm Hg. Urine flow and electrolyte excretion decreased to a greater extent in the hypertensive kidneys, such that at comparable BP these indices of excretory function were not different in the two groups. These observations indicate that the capacity of the contralateral kidney to maintain hemodynamic and glomerular function at reduced BP is compromised severely and suggest the possibility that the impaired autoregulatory capability may contribute to the maintenance of hypertension observed in this model.

Animals↗

PubMedDate not supplied

Bilateral renal function responses to converting enzyme inhibitor (SQ 20,881) in two-kidney, one clip Goldblatt hypertensive rats.

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Animals↗

PubMedDate not supplied

Influence of converting enzyme inhibition on renal hemodynamics and glomerular dynamics in sodium-restricted dogs.

Clearance and micropuncture experiments were performed to evaluate the influence of converting enzyme inhibition (CEI) (SQ 14,225) on renal hemodynamics, glomerular filtration rate (GFR), segmental vascular resistances, and superficial nephron function in anesthetized sodium restricted dogs. In one series (n = 8), renal blood flow (RBF) and GFR exhibited a high degree of autoregulatory efficiency when renal arterial pressure (RAP) was reduced from 126 +/- 5 to 86 +/- 1 mm Hg. With RAP maintained at the reduced level, CEI elicited increases in RBF (3.9 +/- 0.3 to 5.8 +/- 0.5 ml/min per g kw) and GFR (0.81 +/- 0.03 to 0.94 +/- 0.04 ml/min per g kw). With return of RAP to spontaneous levels during continued CEI, RBF and GFR autoregulatory efficiency was maintained, and was similar to that observed in control dogs subjected to the same procedures (n = 5). In the micropuncture experiments (n = 12), RAP was maintained at the reduced level (87.5 +/- .9 mm Hg), and measurements were made before and during CEI. Proximal tubule pressure, peritubular capillary pressure, stop flow pressure, and single nephron GFR (SNGFR) increased significantly. Regression analysis suggested that the increases in SNGFR were associated with small increases in the filtration coefficient. CEI reduced preglomerular resistance by 29% to 35% and efferent arteriolar resistance by 24% to 32%. These results indicate that the increased activity of the renin-angiotensin system that occurs during salt restriction exerts approximately equivalent vasoconstrictor influences on both preglomerular and postglomerular vascular resistance elements.

Animals↗

PubMedDate not supplied

[The regulatory mechanisms of glomerular filtration: the tubuloglomerular feedback system, physiological aspects and their participation in the physiopathology of kidney diseases].

The tubuloglomerular feedback system (TGF), the main component of the autoregulation mechanism, maintains constant glomerular blood flow and filtration rate. The system is based in the morpho-functional association among the macula densa, the afferent and efferent arterioles, the glomerulus and the extraglomerular mesangial cells. The macula densa cells sense the changes in solute concentrations and osmolarity in the tubular fluid and send vasoconstrictor or vasodilatory signals to the arterioles that modify blood flow and glomerular filtration rate. However, the mechanism by which the macula densa sends signals to the arterioles remains unknown. A chemical mediator such as prostaglandins or adenosine has been postulated. Our studies discarded the participation of prostaglandins as mediators. Further studies from our group with adenosine analogs indicate that this nucleotide participates in the activation of the TGF responses, and suggest alternate activation pathways not previously described. To evaluate the role of TGF feedback in the glomerular hemodynamic changes associated with progression of renal damage, we studied TGF responses in rats with Goldblatt hypertension and partial ablation of the contralateral kidney. Our results suggest that the sensitivity of the system is decreased. This alteration may contribute to glomerular hypertension and progression to renal damage.

Adenosine↗