Structural and functional adaptation in the rat myocardium and coronary vascular bed caused by changes in pressure and volume load.
The structural and functional characteristics of the myocardium and coronary vessels are major determinants of cardiac function. Both can be influenced by long-term hemodynamic changes, such as sustained alterations of pressure and/or volume load on the heart. The diastolic pressure-volume relationship of the left ventricle (LV) was evaluated in arrested isolated hearts from spontaneously hypertensive rats (SHR), Wistar Kyoto normotensive rats (WKY), pregnant and hyperthyroid SHR and WKY. Such measurements of the LV dimensions were also performed after antihypertensive therapy by hydralazine, felodipine, metoprolol and alpha-methyldopa. Cardiac function was studied in a perfusion system in which external work could be measured at various pre- and afterloads. Coronary flow and O2-extraction could also be determined. LV function was examined in young and aged SHR and WKY, in metoprolol-felodipine treated SHR and in two-kidney, one clip hypertension before and after its reversal by renal artery unclipping. The SHR LV in early established primary hypertension mainly showed eccentric hypertrophy, with increased LV enddiastolic volume for a given filling pressure and a marginal reduction of wall to lumen ratio (w/ri). Hence, a higher stroke volume could be delivered for a given myocardial fibre shortening. Nevertheless, when challenged by high afterloads, LV function in SHR was considerably augmented compared with WKY. The antihypertensive drugs used reduce arterial pressure in different ways, which may differently affect cardiac design. Generally, the results suggest that wall thickness was structurally adapted to keep w/ri balanced to the prevailing blood pressure, while internal radius was adapted to long-term changes in diastolic filling. Thus sympatholytic drugs which lowered arterial pressure by reducing cardiac output, induced a reduction of wall thickness at a minor change of internal radius, while drugs which reduced pressure by systemic vasodilation increased internal radius, thus reducing w/ri. Further, the results stress the importance also to consider the type of load which causes LV hypertrophy, and how rapidly it is imposed. Thus, renal hypertension was associated with reduced LV performance, despite considerable hypertrophy. However, on reversal of renal hypertension by unclipping, cardiac function was soon enhanced to match the degree of LV hypertrophy as in SHR. This suggests that the renal hypertensive state per se adds some cardio-depressive influence, possibly by inducing reversible changes of cardiac myosin isoenzymes, which tends to offset the improved ventricular performance inherent in LV hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)
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D000222:Adaptation, Physiological / Q000187:drug effects; D000375:Aging; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D006332:Cardiomegaly; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000473:pathology / Q000502:physiology*; D003971:Diastole; D005260:Female; D006321:Heart / Q000502:physiology*; D006977:Hypertension, Renal / Q000503:physiopathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D010477:Perfusion; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents