Development of blood pressure in spontaneously hypertensive rats after withdrawal of long-term treatment related to vascular structure


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Abstract

We have studied the effects of long-term treatment with different antihypertensive drugs on blood pressure and mesenteric resistance vessel structure of spontaneously hypertensive rats (SHR), both during treatment and after withdrawal of treatment. Young SHR were treated from 4 to 24 weeks with five different drugs: perindopril (1.5mg/kg per day), captopril (60mg/kg per day), hydralazine (25mg/kg per day), isradipine (42mg/kg per day) and metoprolol (130mg/kg per day). At 24 weeks, 24-h mean blood pressures (MBP), measured invasively, were 121 mmHg (perindopril), 137mmHg (captopril), 140mmHg (hydralazine), 149mmHg (isradipine) and 146 mmHg (metoprolol), compared to control values of 177 mmHg (SHR) and 132 mmHg (Wistar-Kyoto rats, WKY). Mesenteric resistance vessel structure, measured as media: lumen ratio (m:1), was also reduced to different extents: to WKY-level by perindopril (m:1 = 4.4%), to midway between SHR- and WKY-levels by captopril, hydralazine and isradipine (m: 1 = 5.9%), and not at all by metoprolol (m: 1 = 6.8%). When treatment was discontinued, low MBP (ca 151 mmHg) persisted for 12 weeks in rats treated with the angiotensin converting enzyme inhibitors (perindopril and captopril), but rose rapidly in rats which had received the other treatments. At 3–12 weeks after withdrawal of treatment vascular structure was closely correlated with the blood pressure expected from the SHR- and WKY-control values, as were the left ventricle: body weight ratios. The results suggest that the ability of a drug to control vascular structure during treatment is not in itself a predictor of a persistent effect on blood pressure after withdrawal of treatment. They also pointed to the usual close relationship between vascular structure and blood pressure in the absence of treatment.

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