Prevention of genetic hypertension by early treatment of spontaneously hypertensive rats with the angiotensin converting enzyme inhibitor captopril.

Our purpose was to evaluate whether early treatment of spontaneously hypertensive rats (SHR) with the angiotensin converting enzyme inhibitor captopril could permanently alter the course of hypertension. Mating pairs of SHR were treated with captopril, and their pups were maintained on captopril until experimentation. Some captopril-treated rats were taken off treatment at 2 months of age, and then some of these rats were mated at 3 months of age. The mean arterial pressures of conscious captopril-treated rats, the rats removed from therapy, and the offspring of the rats removed from therapy were significantly smaller than control rats at 4 and 9 months of age. Central administration of angiotensin I or II induced significantly smaller increases in blood pressure and drinking in captopril-treated rats and the rats removed from therapy compared with control rats. The increase in blood pressure in response to intravenous injection of angiotensin I or II was similar among all groups, with the exception that captopril-treated rats showed lesser pressor responses to angiotensin I. Early administration of captopril, even after administration was stopped, prevented the subsequent development of hypertension in SHR and altered the course of development of hypertension in their progeny. This effect was associated with decreased central responses to angiotensin I and II. Our data suggest that captopril may permanently alter the development of hypertension in SHR through an alteration in the central renin-angiotensin system.