Endothelin and nitric oxide interact to regulate stretch-induced ANP secretion

Endothelin and nitric oxide interact to regulate stretch-induced ANP secretion. Am. J. Physiol. 273 (Regulatory Integrative Comp. Physiol. 42): R301-R306, 1997.-The purpose of this study was to determine the nature of the permissive effect of atrial stretch on atrial natriuretic peptide (ANP) secretion and the mechanism for the rapid termination of endothelin (ET) signaling following the removal of ET-dependent stimuli. Basal ANP release was not affected by either an elevation or inhibition of nitric oxide (NO) activity, but stretch-stimulated ANP release was significantly reduced from 144 +/- 20% to -3 +/- 7% of the baseline by increased NO activity. Furthermore, while the response to ET alone at low pressure was 37 +/- 13% of the baseline ANP secretion rate (P > 0.05), this response increased to 137 +/- 27% (P < 0.05) when NO activity was blocked, a response equal to the control high-pressure response (144 +/- 20%). Thus the reduction in NO activity is a permissive effect of stretch, and NO can rapidly terminate an ET-stimulated ANP response. Therefore, stretch-induced ANP secretion is regulated by a reciprocal interaction between locally produced ET, which appears to increase, and NO, which appears to decrease.