Open AccessJournal Article
Effect of central administration of MK-422 (the diacid form of enalapril) on the development of hypertension in the spontaneously hypertensive rat.
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Both captopril and MK-422 prevent the development of hypertension in SHR, presumably by blocking angiotensin-converting enzyme, suggesting that the brain renin-angiotens in system contributes to the pathogenesis of hypertensionIn that model.Abstract:
Intracerebroventricular (i.c.v.) administration of captopril attenuates the development of hypertension in spontaneously hypertensive rats (SHR). To determine whether these effects are related to inhibition of angiotensin-converting enzyme we assessed the effects of chronic i.c.v. administration of MK-422 (a converting enzyme inhibitor chemically unrelated to captopril) on arterial pressure and vascular reactivity in young (seven-week-old) male SHR. MK-422 (0.2 or 1.0 microgram/h, osmotic mini pump) was infused into the lateral ventrical for 4 weeks. Control SHR received artificial CSF i.c.v., or 0.2 microgram/h MK-422 i.v. Vascular reactivity to phenylephrine, vasopressin and direct sympathetic nerve stimulation was assessed in renal and mesenteric vascular beds using miniaturized pulsed Doppler flow probes. MK-422 attenuated the development of hypertension. Arterial pressure at 4 weeks of treatment was: SHR-i.c.v. MK-422 (0.1 microgram/h): 137 +/- 3.4; (1.0 microgram/h): 138 +/- 2.9; SHR i.v. MK-422 176 +/- 4.5 and SHR control: 168 +/- 4.9 mmHg (P less than 0.01). SHR-i.c.v. MK-422 showed significantly attenuated increases in mesenteric vascular reactivity in response to vasoconstrictors, nerves and sympathetic nervous stimulation. Dose and frequency response curves were characterized by a shift to the right and a significant decrease in the slopes. In conclusion, both captopril and MK-422 prevent the development of hypertension in SHR, presumably by blocking angiotensin-converting enzyme, suggesting that the brain renin-angiotensin system contributes to the pathogenesis of hypertension in that model.read more
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Transient AT1 receptor-inhibition in prehypertensive spontaneously hypertensive rats results in maintained cardiac protection until advanced age.
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