S. F. Echtenkamp

Effects of intrarenal infusion of calcium entry blockers in anesthetized dogs.

Renal function and renin release were studied in anesthetized, uninephrectomized dogs during intrarenal infusions of the calcium influx blockers, verapamil and nifedipine. Verapamil increased renal blood flow by 20% (p less than 0.05) but did not alter glomerular filtration rate. Verapamil produced five-to-seven fold increases in urine flow and the rates of excretion of sodium and chloride (p less than 0.01). Significant increases in the rates of excretion of potassium, calcium and magnesium were also observed. Despite its striking effects on renal function, verapamil, in nonhypotensive doses, failed to alter renin secretion. Intrarenal infusion of nifedipine had no consistent effect on renal blood flow or the rate of glomerular filtration but increased urine flow and the rates of excretion of sodium and chloride by more than three fold (p less than 0.01). Nonhypotensive doses of nifedipine had no significant effect on renin release. In dogs with a denervated nonfiltering kidney, an intrarenal verapamil or nifedipine infusion did not produce a significant change in renin release. This study demonstrates a striking effect of calcium entry blockers on the reabsorption of sodium, chloride, and water by the renal tubules in intact dogs but renin release did not increase unless hypotension occurred.

Effects of indomethacin, renal denervation, and propranolol on plasma renin activity in conscious dogs with chronic thoracic caval constriction.

The role of renal prostaglandins and the adrenergie nervous system in the control of rcnin release was studied in conscious dogs with thoracic caval constriction. lndomethacin reduced plasma renin activity (PRA) in intact animals with thoracic caval constriction by 43% but failed to change PRA after surgical renal denervation and during chronic propranolol administration; adrenergie blockade reduced the initial control level of PRA before indomethacin from 15 to 4 ng angiotensin I/ml per hr. Renal hemodynamic function was markedly reduced by indomethacin both before and after adrenergie blockade. These observations indicate that prostaglandins are involved ha the control of renin release, but they appear to have a more important role in the control of renal arterior resistance. The adrenergic nervous system also plays a role in the hyperreninemia of caval constriction and, possibly, a greater role than the renal prostaglandins. In the first experimental design, surgical renal denervation and daily oral propransolol administration in dogs with caval constriction reduced PRA to normal in two of seven dogs and a natriuresis occurred. In four of the five remaining animals, PRA fell, but not to normal, and renal sodium excretion failed to increase. In a second experimental design, the kidneys were denervated and propranolol was given before the dogs were subjected to caval constriction and propranolol was continued for 5 days; PRA increased markedly, sodium retention occurred, and ascites formed. Under these circumstances, compensatory mechanisms secondary to caval constriction led to increased PRA in spite of adrenergie blockade.

Effects of Sodium Chloride on Prostacyclin-Stimulated Renin Release in Dogs with Filtering and Nonfiltering Kidneys:

Abstract The effects of intrarenal infusion of sodium chloride (NaCl) on prostacyclin (PGI2)-stimulated hyperreninemia were examined in groups of anesthetized dogs with either a single filtering kidney or a single denervated nonfiltering kidney, a model in which the renal tubules are damaged, and the macula densa is nonfunctional. After control observations, intrarenal infusion of prostacyclin at nonhypotensive doses resulted in significant increments of renin secretion and renal blood flow (RBF) in both preparations. Superimposition of intrarenal NaCl to the ongoing prostacyclin infusion produced a striking decrease of renin secretion in dogs with a filtering kidney. In contrast, dogs with a nonfiltering kidney failed to show a significant change in renin secretion during intrarenal NaCl administration. Renal blood flow remained unaffected by NaCl in both groups. The increment in renal venous plasma sodium concentration of 18-21 meq/liter was similar in both series. It is proposed that the renin response to intrarenal NaCl was mediated through the renal tubules, since renin secretion failed to decrease in the nonfiltering kidney preparation. Thus, the present results indicate that prostacyclin-stimulated renin secretion was modulated by a tubular mechanism, probably the macula densa.

Failure of indomethacin to inhibit saralasin-stimulated plasma renin activity in conscious dogs with mild sodium depletion.

Abstract The hypothesis that prostaglandins play a role in the angiotensin II control mechanism for renin release was examined by interrupting the short-loop negative feedback of angiotensin II on the JG cells with the competitive angiotensin II antagonist saralasin. Mildly sodium-depleted conscious dogs received either indomethacin, or the vehicle alone followed by an intravenous infusion of saralasin. Saralasin produced equivalent increases in PRA in the vehicle- and indomethacin-treated groups with no detectable change in arterial pressure. Plasma renin activity increased in the indomethacin-treated group despite a 58% fall in the rate of excretion of PGE2. These results suggest that in the conscious dog renal prostaglandins do not play an appreciable role in angiotensin II feedback control of renin release.

Renal prostaglandins, renin release, and renal hemodynamic function in high renin states

Renal prostaglandins play a role in the control of renin release during chronic sodium depletion, during the acute phase of renovascular hypertension and in experimental low output heart failure in conscious dogs. However, with marked inhibition of the renin-angiotensin system, the adrenergic nervous system and the renal prostaglandins, PRA was still 17 times normal during chronic sodium depletion. After blockade of the adrenergic nervous system and the renal prostaglandins, PRA was 10 times normal during the acute phase of one-kidney renovascular hypertension. These findings demonstrate that other important mechanisms, possibly both the renal vascular receptor (so-called baroreceptor) and the macula densa, were involved. Both PGI2 and PGD2 given intrarenally increased renin release in both filtering and nonfiltering kidneys, but PGI2 was more potent than PGD2. Available evidence favors a role of PGI2 and it seems likely that the site of action is on the JG cells. Indomethacin produced a profound drop in CCr and CPAH during sodium depletion and in experimental heart failure which demonstrates an important role for the renal prostaglandins in the control of renal arteriolar tone. An important incidental finding is that renal denervation combined with propranolol administration decreased PRA from very high levels to normal in 50% of the dogs with experimental low output heart failure and a concurrent striking natriuresis occurred.