SELECTIVE DYSREGULATION OF NITRIC-OXIDE SYNTHASE TYPE-3 IN CARDIAC MYOCYTES BUT NOT CORONARY MICROVASCULAR ENDOTHELIAL-CELLS OF SPONTANEOUSLY HYPERTENSIVE RAT

Objective: Recent studies indicate that endothelial type nitric oxide synthase (NOS3) modulates cardiac systolic and diastolic function and the inotropic responsiveness to beta-adrenergic agonists, and may affe ct myocardial oxygen consumption. Although NOS3 is a constitutive prot ein, its levels of expression can be modified by various physiological and pathophysiological stimuli. We investigated whether the cell-spec ific expression of NOS3 mRNA and protein are altered in cardiac hypert rophy. Methods: Left ventricular cardiac myocytes and coronary microva scular endothelial cells were freshly isolated from 12 week old male s pontaneously hypertensive rat (SHR) and matched normotensive Wistar ra t hearts. NOS3 protein levels were assessed by Western analysis, and m RNA levels by RT-PCR and Southern blotting. Results: Left ventricular/ body weight ratios were significantly increased in SHR compared to Wis tar controls, indicating significant hypertrophy. The levels of NOS3 p rotein were markedly decreased in SHR compared to Wistar cardiac myocy tes (by similar to 85%). By contrast, the expression of NOS3 mRNA norm alized for GAPDH was increased similar to 3 fold in SHR cardiac myocyt es relative to Wistar controls. Tn freshly isolated microvascular endo thelial cells, however, levels of NOS3 protein and NOS3 mRNA were simi lar between the two groups. Conclusions: The expression of NOS3 is sel ectively altered in cardiac myocytes but not coronary microvascular en dothelial cells of young SHR hearts, with a marked decrease in NOS3 pr otein but an increase in NOS3 mRNA. This dysregulation of NOS3 could c ontribute to contractile dysfunction in left ventricular hypertrophy. (C) 1998 Elsevier Science B.V. All rights reserved.