Influence of long-term antihypertensive therapy on cardiac function, coronary flow and myocardial oxygen consumption in spontaneously hypertensive rats.

The relationships between cardiac performance, coronary flow, coronary vascular resistance at maximal vasodilatation and myocardial oxygen consumption were determined in isolated hearts from spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto rats (WKY) and from SHR given metoprolol (beta 1-selective blocker) and felodipine (selective calcium antagonist) for 35 weeks. A working heart perfusion system was used. An oxygen electrode allowed continuous measurement of oxygen tension in the venous coronary effluent. Blood pressure was reduced close to normal levels in treated SHR. Treatment also caused a substantial reduction of left ventricular weight. In both treated and untreated SHR, maximal cardiac performance, expressed as peak stroke volume, was enhanced above that of WKY at high perfusion pressures, while performance at low perfusion pressures was clearly reduced in the former groups. At a given workload, myocardial oxygen consumption (mmol O2/min per g) was reduced in both groups of SHR. This suggests a physiological structural adaptation to an elevated cardiac load in hypertension, where more myofibrils contribute to produce a given amount of work and therefore less oxygen is consumed per unit muscle mass. Coronary flow was reduced at any given perfusion pressure and oxygen extraction was increased in untreated SHR versus WKY. By causing regression of hypertensive structural vascular changes, treatment markedly increased coronary flow and correspondingly decreased oxygen extraction. Thus, by enhancing the myocardial nutritional supply with antihypertensive treatment, the reduced cardiac function at low perfusion pressure in untreated SHR was almost normalized.