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Impaired vasodilator and chronotropic responses to 5-hydroxytryptamine in two models of hypertension-associated
M J Mertens1, M Pfaffendorf, P A van Zwieten
1Department of Pharmacotherapy, Academic Medical Centre, Amsterdam, The Netherlands.
Objective:
In connection with hypertension, research concerning 5-hydroxytryptamine (5-HT) receptors and subtypes in the cardiovascular system has so far been predominantly focused on various vascular tissues. In this study, the effects of 5-HT were investigated in isolated hearts with experimental cardiac hypertrophy.
Design And Methods:
Cardiac hypertrophy was induced by stenosing the abdominal aorta (ASR) of 5-week-old Wistar rats. The functional response to serotonin was measured in unpaced, ASR hearts (18-20 weeks) and compared with those of "sham" operated SHR and WKY rats.
Results:
The ASR, less hypertensive than SHR, showed more pronounced cardiac hypertrophy. The positive chronotropic and coronary vasodilator response to 5-HT was reduced in hypertrophied hearts from SHR and ASR when compared to "sham" operated and normotensive controls. The positive chronotropic effect of 5-HT could be antagonised with ketanserin, without affecting the coronary vasodilation. 5-HT did not induce any change in contractile force.
Conclusions:
Cardiac hypertrophy is associated with impaired coronary vasodilator and chronotropic responsiveness to serotonin. The chronotropic response to 5-HT is mediated by the 5-HT2-receptor subtype.