Low-density lipoproteins inhibit histamine and NaNO2 relaxations of the coronary vasculature and reduce contractile function in isolated rat hearts.
In the present study we examined the action of native and oxidized low-density lipoproteins (LDL) on coronary vascular and cardiac function and ultrastructure in rat hearts perfused isovolumically in the Langendorff mode. Responses of the coronary resistance vessels to the endothelium-dependent vasodilator, histamine, and the endothelium-independent vasodilator, NaNO2, were measured together with contractile function (rate-pressure product) before and after perfusion for 20 min with native - or oxidized-LDL at a concentration of 100 mu g protein/ml. Ultrastructural damage was assessed via electron microscopy of perfusion-fixed heart specimens. When compared to findings in untreated, control hearts, both native and oxidized LDL significantly reduced the responsiveness of the coronary resistance vessels to histamine and NaNO2, by about 50%. The rate-pressure product was decreased more by oxidized-LDL (41%) than by native-LDL (26%). Electron microscopy showed no ultrastructural abnormalities in the vasculature or myocytes of control hearts. The administration of both native- and oxidized-LDL caused distortion of endothelial cells, increased levels of pinocytotic vesicles in both endothelial and smooth muscle cells, detachment of blood vessels from surrounding tissue, and some regions of myocyte injury with evidence of mitochondrial injury and fluid accumulation. Our results show that both native- and oxidized-LDL are toxic to the isolated heart preparation. They inhibit coronary vascular responsiveness to vasodilators, reduce contractile function, and produce damage to cardiac ultrastructure.
Harrison
G J
GJ
Rotary Centre for Cardiovascular Research, School of Science, Griffith University, Nathan, Australia.
Jordan
L R
LR
Selley
M L
ML
Willis
R J
RJ
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects* / Q000502:physiology; D003331:Coronary Vessels / Q000187:drug effects* / Q000503:physiopathology; D004347:Drug Interactions; D006632:Histamine / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000009:adverse effects* / Q000494:pharmacology; D008297:Male; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D009206:Myocardium / Q000648:ultrastructure*; D009566:Nitrates / Q000494:pharmacology; D010477:Perfusion / Q000379:methods; D051381:Rats; D017208:Rats, Wistar
D008077:Lipoproteins, LDL; D009566:Nitrates; D006632:Histamine; C031618:sodium nitrate