Adenylate cyclase‐mediated vascular responses of rabbit aorta, mesenteric artery and skin microcirculation

Abstract

The importance of adenylate cyclase‐mediated vascular relaxation in the macro and microcirculation was assessed in rabbit aortic and coeliac artery bioassay rings in vitro and skin microvessels in vivo. The neuropeptide pituitary adenylate cyclase‐activating polypeptide (PACAP38), the β‐agonist, isoprenaline, and the prostaglandins, PGE1 and PGE2, were compared with the activity of nitroprusside, which acts by stimulating guanylate cyclase. In aortic tissue the relative relaxant potencies were (−log m EC50, 100% = response to nitroprusside 10−6 m): nitroprusside 7.0, PACAP38 6.8, isoprenaline 6.3; PGE1 and PGE2 were weak constrictors. In coeliac artery rings relative potencies were (−log m EC50, 100% = response to nitroprusside 10−5 m): PACAP38 6.6, PGE1 6.6, nitroprusside 6.5, PGE2 4.9, and isoprenaline 4.3. Comparative potencies when injected into anaesthetized rabbit skin in vivo were (−log mol/site required to increase blood red cell flux by 75%): PACAP38 13.0, PGE2 10.7, isoprenaline 9.7, PGE1 9.1, nitroprusside < 7. Nitroprusside, the most effective relaxant tested in the aorta, was 107 fold less potent than PACAP in its effect on skin blood flow. PGE1 and PGE2 were constrictors of the aorta, of intermediate effect in the coeliac artery, but potent vasodilators of the microcirculation. In this model, the importance of adenylate cyclase‐mediated vascular relaxation increases with decreasing vessel size. 1993 British Pharmacological Society