pituitrin and pepstatin

The effect of prolonged intracerebroventricular (i.c.v.) infusion of N-acetyl-pepstatin in young and adult spontaneously hypertensive rats was studied. In young animals, pepstatin infusion resulted in a decrease in blood pressure and heart rate. Water intake and body weight were not affected. The depressor effect was accompanied by a slight increase in plasma renin activity and decreases in plasma vasopressin and plasma catecholamines. The blood pressure of adult rats with already established hypertension was not significantly affected. In addition, changes in plasma renin or catecholamines were not observed in these animals while vasopressin levels were slightly increased. The involvement of a possibly decreased sympathetic activity in the depressor effect of pepstatin is suggested. It is concluded that increased brain renin activity contributes to the development of hypertension of spontaneously hypertensive rats.

Topics: Aging; Angiotensin I; Animals; Blood Pressure; Cerebral Ventricles; Heart Rate; Hypertension; Injections, Intraventricular; Kinetics; Male; Oligopeptides; Pepstatins; Rats; Renin; Renin-Angiotensin System; Vasopressins

The specificity of pepstatin A as an inhibitor of the cardiovascular actions of renin injected into anaesthetized rats has been investigated. Pepstatin A 70 micrograms/kg/min partially inhibited the pressor response to injected renin without affecting the pressor responses to injected angiotensin II, phenylephrine or vasopressin. Pepstatin A 150 micrograms/kg/min also produced partial inhibition of injected renin, but in addition caused significant inhibition of the other pressor agents. This was in contrast to the effects of the angiotensin converting enzyme inhibitor captopril, 100 micrograms/kg i.v., which caused greater inhibition of the renin pressor response than pepstatin A without affecting the pressor response to injected angiotensin II, phenylephrine or vasopressin. Finally the direct acting vasodilator hydralazine was found to have a similar non-specific inhibitory effect to pepstatin A on the pressor responses to injected pressor agents. It is concluded that pepstatin A reduces the pressor responsiveness to injected pressor agents and that this non-specific cardiovascular activity limits the usefulness of pepstatin A as a pharmacological tool to inhibit renal renin in vivo.

Topics: Animals; Blood Pressure; Captopril; Female; Hydralazine; Oligopeptides; Pepstatins; Phenylephrine; Rats; Rats, Inbred Strains; Renin; Swine; Time Factors; Vasopressins