ANGIOTENSIN-II INCREASES CGMP CONTENT VIA ENDOTHELIAL ANGIOTENSIN-II AT1 SUBTYPE RECEPTORS IN THE RAT CAROTID-ARTERY

Angiotensin II (Ang II) has been reported to modulate cGMP formation in various types of cells. To acquire direct information on the intracellular transduction involved in this mechanism, we tested the effects of Ang II on vascular tone and on cGMP content of in vitro isolated carotid arteries from 12-week-old Wistar-Kyoto rats. Segments of carotid artery 20 mm long (n=8 for each group) maintained at a transmural pressure of 100 mm Hg were immersed in a bath (38 degrees C) containing oxygenated Tyrode's solution. At the end of each experiment, the vessel diameter was measured, and the wall cGMP content was determined by enzyme immunoassay. Under basal conditions, mean diameter was 968+/-19 mu m, and mean cGMP carotid artery content was 38.9+/-3.5 fmol/mg tissue. Incubation for 20 minutes with Aug II (10(-5) mol/L) significantly increased cGMP wall content, twofold above the basal content (P<.O1), and constricted the vessel (60+/-2.2% of the control diameter, P<.001). After preincubation with a nonselective antagonist of Ang II receptors, saralasin ([Sar(1),Val(5),Ala(8)]Ang II, 5x10(-5) mol/L), or with a specific antagonist of Ang II AT1 receptor subtype, losartan (5x10(-5) mol/L), carotid diameter and cGMP content were no longer affected by Ang II. Exposure of carotid arteries to a specific antagonist of Ang II AT2 receptor, PD 123319 (10(-7) mom), modified neither Ang II-induced diameter decrease nor cGMP content increase. Constriction of the vessel with KCl (26+/-3%, P<.001) did not modify the basal cGMP wall content. Endothelium removal or incubation with N-G-nitro-L-arginine methyl ester (10(-3) mol/L) reduced the cGMP content (22+/-9%, P<.05 and 20+/-11%, P<.05, respectively); Ang II further decreased the diameter (P<.001) but no longer increased the cGMP content under these experimental conditions. The present study shows that Ang II constricts the carotid artery and increases cGMP level specifically via the Ang II AT1 receptor subtype in in vitro intact rat carotid artery. The mechanism underlying this increase in cGMP is thought to be mediated through endothelial NO synthase stimulation by Ang II.