Antihypertensive drug therapy prevents cerebral microvascular abnormalities in hypertensive rats.
Studies were performed on anesthetized 16-18 week old normotensive Wistar-Kyoto rats, spontaneously hypertensive rats, and Goldblatt two-kidney one clip renal hypertensive rats, treated from age 4-5 weeks with an oral antihypertensive regimen consisting of hydralazine, reserpine, and chlorothiazide. Measurements of flow and intravascular pressure in the cerebral microvasculature were made via a constantly suffused open cranial window using video microscopy. A significant upward shift was seen in the pressure range for cerebral blood flow autoregulation in both groups of untreated hypertensive animals. Following treatment, the autoregulatory range in both hypertensive models was restored to a level nearly identical to control. The prevention of this shift in treated animals was due primarily to the prevention of structural microvascular adaptations that occur in untreated hypertensive animals. By preventing elevations in microvascular pressure, treatment may have eliminated the major stimulus for development of hypertrophy in resistance vessels. However, a persistent increment of arteriolar wall mass in treated spontaneously hypertensive rats may represent a hyperplastic response not influenced by treatment. Likewise, a persistent constriction of the smallest arterioles in treated renal hypertensive rats may represent a differential sensitivity of microvessels to circulating vasoactive agents. It appears that treatment initiated in the prehypertensive state, or before significant sustained hypertension has occurred, can markedly reduce the cerebrovascular morbidity associated with two different forms of hypertension.
D000222:Adaptation, Physiological / Q000187:drug effects; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001783:Blood Flow Velocity / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D002561:Cerebrovascular Disorders / Q000209:etiology / Q000517:prevention & control*; D002740:Chlorothiazide / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D006830:Hydralazine / Q000627:therapeutic use; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D006977:Hypertension, Renal / Q000150:complications / Q000188:drug therapy; D006978:Hypertension, Renovascular / Q000150:complications / Q000188:drug therapy; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY; D012110:Reserpine / Q000627:therapeutic use
D000959:Antihypertensive Agents; D006830:Hydralazine; D002740:Chlorothiazide; D012110:Reserpine