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Effect of chronic dihydropyridine (Isradipine) on the large arterial walls of spontaneously hypertensive rats
The effect of genetic hypertension and of chronic therapy by calcium entry blocker (CEB, isradipine) on the function and structure of large arteries has been studied in adult spontaneously hypertensive rats (SHR, n = 30) and in their normotensive control Wistar-Kyoto (WKY) rats (n = 30). Fifteen-wee...
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Published in: | Circulation (New York, N.Y.) N.Y.), 1994-12, Vol.90 (6), p.3024-3033 |
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Main Authors: | , , , , |
Format: | Article |
Language: | English |
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Summary: | The effect of genetic hypertension and of chronic therapy by calcium entry blocker (CEB, isradipine) on the function and structure of large arteries has been studied in adult spontaneously hypertensive rats (SHR, n = 30) and in their normotensive control Wistar-Kyoto (WKY) rats (n = 30).
Fifteen-week-old rats were randomly allocated to treatment with isradipine (3 mg/kg subcutaneously once a day) or to placebo and followed for 12 weeks. Hemodynamic parameters, including instantaneous pressure and aortic velocity, were recorded under anesthesia at the end of the treatment period. Passive mechanical properties of carotid arteries were measured in situ in the presence or the absence of smooth muscle cell activity (potassium cyanide poisoning). Histomorphometric parameters of the carotid and aortic media, including cross-sectional area, medial thickness, nucleus density and size, and medial contents of proteins of interstitial matrix, were measured by an automated morphometric system. Untreated SHRs had greater peripheral resistance, stiffer and thicker arterial walls because of smooth muscle cell hyperplasia (thoracic aorta and carotid artery) and/or hypertrophy (thoracic aorta), and increased collagen content than did normotensive control rats. SHRs showed a significant left ventricular hypertrophy. For the whole duration of treatment, treatment with CEB normalized the arterial pressure in SHRs. We observed a significant decrease in peripheral resistance, increased cardiac output, and left ventricular contractility without significant reduction in left ventricular hypertrophy. Increases in diuresis and natriuresis were associated during the last week of treatment in both treated strains with marked increase in plasma renin activity; in contrast, urinary aldosterone was increased by treatment in WKY rats but not in SHRs. Arterial compliance was significantly increased by CEB under control and passive conditions. CEB induced a significant reduction in the medial hypertrophy of the aortic walls of SHRs and WKY rats associated with a reduction in medial hyperplasia. In the carotid artery, CEB reduced smooth muscle cell hypertrophy but did not affect the smooth muscle cell hyperplasia. Isradipine significantly reduced the arterial wall collagen contents in both strains, with marked increases in the elastin content in the carotid but not in the aortic wall.
These results suggest that (1) despite normalization of arterial pressure, chronic treatment with CEB in SHR |
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ISSN: | 0009-7322 1524-4539 |
DOI: | 10.1161/01.cir.90.6.3024 |