Angiotensin II-Induced Relaxation of Vascular Smooth Muscle

Abstract

The effects of angiotensin II (All) on contractile tension were studied in vascular smooth muscle from dogs, pigs and rabbits. Helically cut strips of renal veins were mounted in organ chambers and isometric contractions were recorded. Contraction of the venous strips was induced by application of 10^–8 g/ml norepinephrine (NE). Subsequent addition of 5 × 10^-8 g/ml All caused a triphasic response: (1) there was an initial contraction (subsequent contractions were tachyphylactic in all species); (2) the contraction was followed by a relaxation below the contraction induced by NE (subsequent relaxation responses were tachyphylactic in dog and pig veins), and (3) there was a return from the relaxation to the level of the NE-induced contraction. The duration of the entire response was approximately 5 min. The magnitude of the relaxation varied inversely with the level of the NE contraction when the contractile state was altered by changing the NE concentration. Conditions which inhibit the sodium pump (potassium-free solution and ouabain) and beta-adrenergic blockade with pro-pranolol had no effect on the All-induced relaxation. The relaxation was temperature sensitive. Inhibitors of prostaglandin synthesis (indomethacin and aspirin) and saralasin attenuated the relaxation in response to AIL Prostaglandins E₁ and E₂ and arachidonic acid caused relaxation of renal vein strips contracted with NE; the relaxant effect of arachidonic acid was blocked by indomethacin. These results suggest that: (1) All stimulates the synthesis of prostaglandins in isolated venous smooth muscle, and (2) endogenous prostaglandins modulate the response of venous smooth muscle to AIL