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 urinary protein excretion (14 +/- 2 v 63 +/- 16 mg/day at 11.7 weeks of age, P less than .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 less than .01) or Wistar-Kyoto rats (3.5 +/- 1.0 ng Ang I/mL/h, P less than .01) maintained on standard diet and water.(ABSTRACT TRUNCATED AT 250 WORDS)
Stier
C T
CT
Department of Pharmacology, New York Medical College, Valhalla 10595.
Chander
P
P
Gutstein
W H
WH
Levine
S
S
Itskovitz
H D
HD
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002216:Captopril / Q000008:administration & dosage / Q000627:therapeutic use*; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D004656:Enalapril / Q000627:therapeutic use; D006321:Heart / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D007022:Hypotension / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D011188:Potassium / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012083:Renin / Q000097:blood; D012307:Risk Factors; D012964:Sodium / Q000652:urine
D004656:Enalapril; D002216:Captopril; D012964:Sodium; D012083:Renin; D011188:Potassium