MK 421 and prevention of genetic hypertension development in young spontaneously hypertensive rats.

MK 421, at the dose of 25 mg/kg, administered daily by gavage to spontaneously hypertensive rats (SHRs) from their 4th to 15th weeks of age almost completely inhibited development of genetic hypertension. Since heart rate and cardiac and systolic indexes were not affected by the drug, prevention of genetic hypertension development was solely related to an early, potent and long-lasting reduction of the progressive increase of the peripheral resistance which generally develops in SHRs during ageing. MK 421 reduced body growth but did not modify fluid intake, plasma NA+ and urine volume, thus water and salt retention did not develop. MK 421 enhanced vascular responsiveness to norepinephrine and angiotension II and reduced myocardial hypertrophy. Plasma renin concentration was increased and urinary antidiuretic hormone did not change. Finally, MK 421's preventive effects against genetic hypertension development persisted up to 10 weeks after discontinuation of treatment.