Mechanism of action of nitrates. Role of changes in venous capacitance and in the left ventricular diastolic pressure-volume relation.
Nitroglycerin, when administered to patients with heart failure, causes a marked reduction in left ventricular filling pressure but often an increase in stroke volume and stroke work; based on the Frank-Starling principle, such a reduction in "preload" would be expected to result in a decrease in left ventricular end-diastolic volume and, therefore, a decline in stroke volume. Assessment of pressure-volume coordinates, however, has revealed that nitroglycerin produces a downward shift in the pressure-volume relationship. This apparent improvement in left ventricular compliance cannot be attributed to alterations in the elastic properties of the myocardium but rather appear to reflect a reduction in left ventricular external constraint. Recent animal and clinical investigations in our laboratory suggest that nitroglycerin causes venous dilatation (particularly in the mesenteric bed), thereby decreasing venous pressure at any given vascular volume. This decrease in cardiac filling pressure results in a decrease in heart size and, therefore, a reduction in pericardial pressure. Left ventricular transmural (intracavitary minus pericardial) pressure is little changed, however, so that end-diastolic volume and stroke volume are maintained.
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009566:Nitrates / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology* / Q000627:therapeutic use; D013318:Stroke Volume / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D009566:Nitrates; D005996:Nitroglycerin