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

Abstract

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)

AT1receptor antagonism attenuates target organ effects of salt excess in SHRs without affecting pressure

“…Thus, our data confirm previous findings in reports demonstrating the cardioprotective action of RAS inhibition in hypertensive rats on a salt excess diet (14,18,33). It reflected decreased LV collagen deposition in treated salt-loaded rats.…”

“…Moreover, in addition to its hemodynamic effects, dietary salt excess exerts additional nonpressure-related cardiac effects in different forms of experimental and human essential hypertension (5-7, 12, 13, 24, 26, 43). Various mechanisms have been suggested to explain these adverse cardiovascular effects of dietary salt excess, and some evidence supports the role of the renin-angiotensin system (RAS) in their development (18,21,33,36,45).…”

Stroke Reduction in Hypertensive Adults With Cardiac Hypertrophy Randomized to Losartan Versus Atenolol

“…In stroke-prone hypertensive rats, di- minishing RAS activity with potassium, 24 captopril, 25 or losartan 26,27 prevented stroke occurrence without lowering blood pressure. Moreover, studies in a model of acute stroke induced by carotid ligation in gerbils suggest that AT 2 receptor stimulation may mediate cerebrovascular anti-ischemic effects.…”

Chronic angiotensin-(1–7) prevents cardiac fibrosis in DOCA-salt model of hypertension

“…Support for this concept comes from clinical trials demonstrating that treatment of hypertensive patients with either angiotensin-converting enzyme (ACE) inhibitors (38, 53) or ANG II type 1 (AT 1 ) receptor blockers (41, 60) provides significant protection from, and even reversal of, end-organ damage. Animal studies have also demonstrated that ACE inhibitors and AT 1 receptor antagonists prevent cardiovascular injury (23,55,56) as well as protect against renal (3, 55, 57) and cerebral (55-57) injury.The use of these antagonists of the RAAS not only reduces the formation and actions of ANG II but also results in a significant elevation of another fragment of the RAAS, angiotensin- …”

“…tagonists prevent cardiovascular injury (23,55,56) as well as protect against renal (3,55,57) and cerebral (55)(56)(57) injury.…”