Atrial natriuretic peptide relaxes arterial basal tone induced by coarctation hypertension

Abstract

We have investigated the vasorelaxant effect of atrial natriuretic peptide (ANP) on isolated non-contracted aorta from coarctation hypertensive rats (HR) and the role of endothelium in this vasorelaxant action. After 7–14 days of surgery, mean blood pressure was higher ( P < 0.01) in HR compared with sham operated rats (SR), used as the control. ANP (10 −6 mol/l) significantly lowered basal tone in previously unstimulated HR thoracic aortic rings; however, it had no effect in HR abdominal aorta or in SR abdominal and thoracic aorta. Endothelial destruction potentiated the vasorelaxant effect of ANP on basal tone in HR thoracic aorta. A similar potentiation of the ANP-response was observed by pre-treatment with N G-nitro- l-arginine methyl ester ( l-NAME, 3 × 10 −4 mol/l) or methylene blue (2 × 10 −5 mol/l) in unrubbed HR thoracic aorta. Treatment with calcium-free Krebs + EGTA (2 × 10 −3 mol/l) + sodium nitroprusside (10 −5 mol/l) or calcium-free Krebs significantly decreased basal tone and abolished ANP-response. These effects were observed only in HR thoracic aorta. Similarly, staurosporine (10 −7 mol/l) and calphostin C (10 −6 mol/l), inhibitors of protein kinase C (PKC), diminished basal tone and abolished the ANP-response in HR thoracic aorta. Acetylcholine (10 −6 mol/l) had a small but significant action on the basal tone of unrubbed HR thoracic aorta. These results demonstrate that ANP has a vasorelaxant effect on aortic basal tone when the vessel is exposed to high blood pressure. Inhibition of ANP effects on basal tone by calcium-free Krebs and PKC antagonists suggests that the HR aorta increases Ca 2+-active tone, that modifies the response of vascular smooth muscle to the vasodilating hormone ANP.