Therapeutic Benefit of Captopril in Salt-Loaded Stroke-Prone Spontaneously Hypertensive Rats Is Independent of Hypotensive Effect

In the present study we examined whether the angiotensin I converting enzyme inhibitor, Captopril, would protect stroke-prone spontaneously hypertensive rats (SHRSP) from stroke and renal pathology over a 26-week period. In the control group of six untreated SHRSP fed Stroke-Prone Rodent Diet and 1% NaCl drinking solution, all animals developed severe hypertension and stroke by 16.1 weeks of age. In eight salt-loaded SHRSP treated with oral Captopril (50 mg/kg/day) beginning at 8.4 weeks of age, systolic blood pressure was slightly but temporarily suppressed and then continued to rise; by 12 weeks of age systolic blood pressure reached levels of severe hypertension, 240 ± 8 mm Hg, and did not differ from that of untreated SHRSP. No deaths or brain lesions were noted in captopril-treated SHRSP despite severe hypertension maintained through 26 weeks of age when the study ended. Captopril treatment prevented increases in urinaryprotein excretion (14 ± 2 υ 63 ± 16 mg/day at 11.7 weeks of age, P < .01) and the severe brain, renal, and cardiac vascular lesions observed in untreated SHRSP. When maintained on Stroke-Prone Rodent Diet and saline, plasma renin activity of untreated SHRSP surviving until 14.5 weeks of age was markedly increased (29.1 ± 9.4 ng Ang I/mL/h) compared with either untreated SHRSP (9.2 ± 2.5 ng Ang I/mL/h, P < .01) or Wistar-Kyoto rats (3.5 ± 1.0 ng Ang I/mL/h, P < .01) maintained on standard diet and water. Our results indicate that chronic Captopril therapy exerts protective effects against stroke and severe vascular lesions in the kidney and heart of saline-drinking SHRSP independent of its hypotensive effect. Interference with the renin-angiotensin system could be a factor in the protective effects of angiotensin converting enzyme inhibitor treatment. Am J Hypertens 1991;4:680-687