Key Points
- To evaluate the long-term antihypertensive efficacy and hormonal mechanisms of the novel converting-enzyme inhibitor YS 980 in stroke-prone spontaneously hypertensive rats.
- Administered oral YS 980 at 50 mg/kg/day for three months to 7-week-old stroke-prone spontaneously hypertensive rats (SHR-sp) and normotensive Wistar Kyoto (WKY) controls.
- Monitored blood pressure, heart rate, plasma renin, angiotensin I and II, norepinephrine, and urinary excretion of aldosterone, electrolytes, and kallikrein.
- Tested vascular and central responsiveness by challenging animals with intravenous and intracerebroventricular injections of angiotensin I and bradykinin.
- Chronic YS 980 administration markedly delayed hypertension onset in SHR-sp and lowered systolic pressure in WKY rats without altering heart rate.
- Plasma renin and angiotensin I increased while urinary aldosterone decreased in both strains, but circulating angiotensin II was not reduced and norepinephrine increased in SHR-sp.
- Pressor responses to intravenous angiotensin I were blunted and depressor responses to bradykinin were enhanced in both strains, whereas central angiotensin I pressor responses decreased only in WKY rats.
Structured PICO
PPopulation7-week-old stroke-prone spontaneously hypertensive rats (SHR-sp) and age and sex-matched normotensive Wistar Kyoto (WKY) rats
IInterventionConverting-enzyme inhibitor (CEI) YS 980 (50 mg/kg/day) administered orally for three months
OOutcomeBlood pressure (development of hypertension)surrogate
The novel converting-enzyme inhibitor YS 980 is a potent blood pressure-lowering compound in stroke-prone spontaneously hypertensive rats, with mechanisms extending beyond simple plasma renin-angiotensin or sympathetic nervous system inhibition.