Coronary reserve in experimental myocardial hypertrophy.
Three types of dysfunction of the coronary circulation have been described in experimental models of hypertension associated with left ventricular hypertrophy: (1) reduced coronary reserve, (2) a relative decrease in perfusion of subendocardial layers, (3) a shift to the right, i.e. to higher pressures, of the circulation pressure autoregulation range. These abnormalities are also observed in hypertensive patients, although it is significant that they do not appear to be related to the extent of left ventricular hypertrophy. The exact causes of these abnormalities have yet to be elucidated. Left ventricular hypertrophy does not seem to be an essential factor, although in certain experimental models of hypertension, there does appear to be a mismatch between the development of the coronary vasculature and hypertrophy of the myocytes. The stresses in vessels due to the increase in systolic, and especially intraventricular diastolic pressure can be viewed as additional aggravating factors. The essential abnormalities are structural and/or functional alterations in arterial walls. The structural alterations are reflected by a narrowed lumen due to parietal thickening. This may result from growth of muscle fibres (hypertrophy or hyperplasia) or collagen tissue and/or remodelling of tissues with no overall change in mass. Functionally, the reduced ability of the arteries to stretch, resulting from endothelial alterations may also play a role in the abnormalities observed in hypertensive patients. In our studies, we examined the effect of the antihypertensive drug perindopril on the coronary circulation in renovascular hypertensive rat (two kidneys--1 clip). We found that this inhibitor of angiotensin converting enzyme (ACE) led to a regression of left ventricular hypertrophy with a return to normal of the coronary reserve. Other studies using either this model or the spontaneously hypertensive rate has also pointed to a beneficial action of ACE inhibitors and other antihypertensive agents on the coronary circulation with reversal of the structural alterations in arterioles. Coronary disease is the main cause of mortality in hypertensive patients. Ironically, antihypertensive therapy has yet to live up to its promise of reducing significantly either the incidence or severity of coronary disease in such patients. Specific alterations of the coronary circulation may account for the relative failure of antihypertensive drugs, despite their proven efficacy in other systems (e.g., stroke prevention). The coronary circulation is unique in certain important respects. It is tightly regulated, maintaining an almost constant flow rate over a wide range of aortic arterial pressures (40-160 mmHg). Extraction of oxygen by the myocardium is almost maximal under resting conditions, and so the circulatory reserve depends almost entirely on the capacity to increase blood flow. This reserve is quite large since there may be a 4 to 5-fold increase in coronary flow rate in response to effort. Another significant detail is that myocardial contraction may lead to an interruption of coronary flow, especially in the deep subendocardial layers, which thus tend to be perfused solely during diastole. This last factor can be seen as the Achilles heel of the coronary circulation, which may be severely limited by myocardial hypertrophy, especially in patients with hypertension.
Gosse
P
P
Centre Hospitalier Universitaire, Chu Bordeaux, France.
Clementy
J
J
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D006332:Cardiomegaly / Q000503:physiopathology*; D003326:Coronary Circulation; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D006978:Hypertension, Renovascular / Q000188:drug therapy / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000503:physiopathology; D007211:Indoles / Q000627:therapeutic use; D009200:Myocardial Contraction; D020913:Perindopril; D051381:Rats
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D007211:Indoles; D020913:Perindopril