Attenuation of the development of spontaneous hypertension in rats by chronic central administration of captopril.
Captopril infused into the lateral ventricle (ICV) of adult spontaneously hypertensive rats (SHR) decreases blood pressure. The current study was designed to explore the effects of brain converting-enzyme inhibition in young animals before the development of established hypertension and to characterize changes induced by captopril in a variety of pressor systems that might be responsible for the development of hypertension in this strain. Captopril (1.25 micrograms/0.5 microliter/hr) was infused into male SHR starting at 7 weeks of age. Four weeks later systolic blood pressure was only 157 +/- 3.3 compared to 181 +/- 3.9 mm Hg in vehicle-infused controls, and the pressor effect of ICV-injected angiotensin I was attenuated by 50%. When the same dose of captopril was infused intravenously, hypertension progressed as in vehicle-treated rats. Serum angiotensin-converting enzyme activity (SACE) and plasma arginine vasopressin (AVP) concentration were significantly higher (p less than 0.001 and 0.05, respectively), in the ICV captopril group than in the ICV vehicle group, while plasma aldosterone concentration and renin activity, fluid intake, urine volume, and urinary sodium excretion were similar in the two groups. Peripheral sympathetic nervous system activity assessed in the resting state was not altered by captopril treatment. In addition, AVP content of the telencephalon, diencephalon, mesencephalon, and pons medulla were not altered by ICV captopril. Renin activity was elevated in the telencephalon of ICV captopril-treated animals but unaltered in the other brain regions examined. These data demonstrate that ICV administration of captopril attenuates the development of hypertension in young SHR by mechanisms apparently independent of altered fluid and sodium balance and the sympathoadrenal system. The effect on blood pressure occurs in the absence of changes in renin activity or AVP content of plasma or those brain regions most often associated with blood pressure control.
D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001127:Arginine Vasopressin / Q000032:analysis / Q000097:blood; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry; D002216:Captopril / Q000008:administration & dosage* / Q000494:pharmacology; D002490:Central Nervous System / Q000187:drug effects; D003681:Dehydration / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D010525:Peripheral Nerves / Q000187:drug effects; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D012084:Renin-Angiotensin System; D012964:Sodium / Q000378:metabolism
D000806:Angiotensin-Converting Enzyme Inhibitors; D001127:Arginine Vasopressin; D011392:Proline; D002216:Captopril; D012964:Sodium