title: Angiotensin II is a necessary component for the development of hypertension in the two kidney, one clip rat.
abstract: The current study was undertaken to define the role of the renin-angiotensin system in the development of hypertension in the two kidney, one clip Goldblatt rat. Captopril was administered orally (100 mg/kg/day) to two groups of rats (n = 8 each) 24 hours before and each day after unilateral renal artery clipping (0.2 mm internal diameter): the drug was given for either 16 weeks (group I) or 24 weeks (group II). Sham-operated (n = 5) and Goldblatt (n = 8) rats not receiving captopril were prepared for comparisons of plasma renin activity and systolic blood pressure. Indomethacin (20 mg/kg/day subcutaneously) was administered for 48 hours concomitantly with captopril to the rats in group I. In group II, systolic blood pressure was monitored for 7 weeks after cessation of captopril. Continual captopril administration to Goldblatt rats completely prevented the rise in systolic blood pressure, a rise that was observed in Goldblatt rats not receiving captopril. Whereas systolic blood pressure of captopril-treated rats approximated 100 mm Hg throughout the study, that of Goldblatt rats not receiving the drug increased to nearly 180 mm Hg within 6 weeks after clipping. Systolic blood pressure of sham-operated rats remained normal. Indomethacin did not change systolic blood pressure in the drug-treated rats in group I. On cessation of captopril therapy in group II, systolic blood pressure increased gradually in a manner that paralleled the development of the disease in the Goldblatt rats that did not receive captopril. Plasma renin activity was determined in Goldblatt and sham-operated rats at either 16 weeks (group I) or 24 weeks (group II) after clipping; the rats from either group with mild hypertension (systolic blood pressure less than 180 mm Hg) had normal plasma renin activity whereas those with severe hypertension (systolic blood pressure greater than 180 mm Hg) had greatly elevated plasma renin activity. In summary, captopril can completely prevent the increase in systolic blood pressure for up to 24 weeks in Goldblatt rats, and this hypotensive effect is not mediated by the prostaglandins. It is concluded that the renin-angiotensin system is a necessary component of the hypertensive process in this experimental model.
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D006977:Hypertension, Renal / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000804:Angiotensin II; D002216:Captopril; D012083:Renin