The Effect of Diazepam Upon the Development of Hypertension in the Spontaneously Hypertensive Rat

Abstract

Summary: The long term antihypertensive effects of the chronic administration of diazepam (D) beginning in the newborn period to spontaneously hypertensive rat (SHR) is the subject of this study. The following treatment groups were investigated: SHR-D = SHR treated with diazepam; SHR-V = SHR treated with diazepam vehicle; WKY-D = Wistar Kyoto control rat (WKY) treated with diazepam; WKY-V = WKY treated with vehicle. Treatment was begun on the 1st day of life. Injections of the following agents were made during hindquarter perfusion: norephinephrine bitartrate, epinephrine hydrochloride, angiotensin-II, barium chloride, and acetylcholine. SHR-V had persistent, progressive hypertension. The blood pressure of SHR-D rose slowly, but did attain levels higher than pressures of either WKY groups. In response to diazepam, the vascular resistance of SHR-D was reduced in comparison to SHR-V. SHR showed significantly greater vascular responses to catecholamines as compared to WKY. These enhanced vascular responses were reduced, but not abolished, by diazepam. When diazepam was administered to adult SHR with established hypertension, the blood pressure was not reduced. No decrease in vascular reactivity was found. In conclusion, treatment from birth with diazepam exerts a profound effect upon the development of high blood pressure and elevated vascular resistance in SHR. Only the young prehypertensive animals treated chronically were responsive to diazepam. The major effect of diazepam may be mediated via generalized depression of vascular smooth muscle responsiveness.

Speculation: Early pharmacologic intervention in young animals, genetically predisposed to severe hypertension, blunts the expression of the disease. This suggests that prehypertensive animals have alterations that can be pharmacologically modified. Vascular smooth muscle may be the common pathway of action for these agents.

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