Increased Activity of Constitutive Nitric Oxide Synthase in Cardiac Endothelium in Spontaneous Hypertension

Abstract

Background We analyzed the activity of nitric oxide synthase in the rat heart to study whether this activity is affected by high blood pressure. Hearts from young (3 to 4 weeks old) and adult (15 to 25 weeks old) Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were excised and frozen in liquid nitrogen. The activities of Ca 2+ -dependent (cNOS) and Ca 2+ -independent (iNOS) were determined in homogenized tissues by measuring the conversion of [ 14 C]- l -arginine to [ 14 C]- l -citrulline in the presence or absence of either EGTA (1 mmol/L) or EGTA plus N G -nitro- l -arginine methyl ester (L-NAME, 1 mmol/L each). Methods and Results Arterial pressure was higher in adult SHR than in young SHR and WKY rats of both ages ( P <.01). The cNOS activity was two to three times higher in hypertensive than in normotensive hearts ( P =.01 to P =.04). No significant activity of iNOS was detected in any tissue. Studies of the right and left ventricles demonstrated a higher cNOS activity in the left sides of the hearts of adult SHR ( P <.05). No differences were found in hearts from WKY rats. Selective removal of endocardial or coronary endothelial cells in hearts of SHR and WKY rats substantially reduced cNOS activity ( P <.01). Conclusions The cNOS activity is upregulated in cardiac endothelial cells of genetically hypertensive rats. The high activity of cardiac cNOS is related to increased arterial pressure of these animals. We propose that in the heart, endothelial cells respond with a higher production of nitric oxide as a compensatory mechanism against high blood pressure and its damaging effects in this organ.