Effects of Nitric Oxide Synthesis Inhibition on the Depressor Response of Atrial Natriuretic Peptide in Rats

BACKGROUND AND OBJECTIVES: It has been suggested that nitric oxide (NO) and atrial natriuretic peptide (ANP) share a final common pathway for vascular smooth muscle relaxation. The aim of the present study was to determine the role of NO on the hypotensive and vasorelaxant effects of ANP. MATERIALS AND METHODS: Sprague-Dawley rats weighing 250-300 g each were anesthetized with thiopental (50 mg/kg IP). The femoral artery was cannulated and the arterial blood pressure and heart rate were continuously monitored in the anesthetized rats (n=19). ANP was administered into the jugular vein after L-NAME treatment. In vitro experiments were performed on intact and endothelium-denuded isolated thoracic aortic rings (n=51) in the presence of either L-NAME or methylene blue. RESULTS: Intravenous administration of ANP (5 ug/kg bolus and 0.2 ug/kg/min infusion) caused a decrease in the mean arterial pressure. L-NAME-pretreatment (1 mg/kg) suppressed the depressor response of ANP. In vitro, the ANP caused a dose-dependent relaxation, and the relaxation response to ANP was attenuated by L-NAME (10-4 M). Endothelium removal or methylene blue (10-5 M) also inhibited the ANP-induced vascular relaxation. CONCLUSION: These results suggest that the hypotensive and the vasorelaxant effect of ANP are, at least in part, NO-dependent.

Influence of Vascular Endothelium in Contraction Induced by Phorbol Ester in Renal Hypertensive Rats

BACKGROUND AND OBJECTIVES: The vascular endothelium plays an important role in circulation, by modulating the contractile responses of the arterial smooth muscle. This study was aimed at investigating the possible role of the endothelium in the contractile response to phorbol 12, 13-dibutyrate (PDB) in chronic two-kidney, one clip (2K1C) hypertensive rats. MATERIALS AND METHODS: 2K1C hypertension was induced by clipping the left renal artery of the study rats, with age-matched rats receiving a sham treatment, which served as controls. The thoracic aortae were mounted in tissue baths to measure the isometric tension. RESULTS: The PDB showed a dose-dependent contraction, with larger responses in the 2K1C hypertensive than the sham-clipped control rats. Nw-nitro-L-arginine (L-NNA) and methylene blue (MB) induced an increase in the tension in the presence of PDB, and the potentiating effects of L-NNA or MB were attenuated in the 2K1C rats as compared to the controls. Staurosporine, an inhibitor of protein kinase C, completely inhibited the contractile response to PDB, as well as enhancing the effects of L-NNA and MB. Removal of the endothelium abolished the contractile responses to L-NNA and MB in both the 2K1C and control rats. The relaxation responses to acetylcholine in the aortic rings precontracted with PDB were also attenuated in the 2K1C rats, and L-NNA prevented the effect of the acetylc-holine-induced relaxation. Indomethacin, glibenclamide and iberiotoxin did not affect the PDB responses in both the 2K1C and control rats. CONCLUSION: These results indicate the endothelium plays an inhibitory role against PDB-induced contraction in rat aortae, by releasing nitric oxide, and the inhibitory role of the endothelium is impaired in 2K1C renal hypertension.