Characterization of the angiotensin II-receptor subtype in the longitudinal smooth muscle of the rat portal vein

Summary

The purpose of the present study was to identify the angiotensin II-receptor subtype involved in the enhancement of the amplitude of the phasic contractions by angiotensin II in the isolated rat portal vein preparation.

At an extracellular Ca²⁺ concentration of 0.9 mmol/l and a K⁺ concentration of 4 mmol/l, angiotensin II induced concentration-dependent increases in the amplitude of the phasic contractions. The enhancement of phasic contraction amplitude caused by angiotensin II was not significantly altered by pretreatment of the rat portal vein with indomethacin 10⁻⁵ mol/l or nitro-L-arginine 10⁻⁴ mol/l, indicating that neither prostaglandins nor the endothelium derived-relaxing factor (NO) are involved. Losartan (DuP 753), a nonpeptide selective AT₁-receptor antagonist, concentration-dependently shifted the concentration-response curve for the effect of angiotensin II on the amplitude of the contractions to the right, without reducing the maximal response (pA₂ = 8.6, slope = 0.98), thus suggesting competitive antagonism at the level of AT₁-receptors. By contrast, PD 123177, a nonpeptide selective AT₂-receptor antagonist, even at 10⁻⁵ mol/l, caused no significant change of the phasic myogenic response to angiotensin II, indicating the absence of AT₂-receptor involvement. Dithiothreitol, a disulfide-reducing agent which is known to inactivate AT₁-receptors in various tissues, markedly inhibited (3 mmol/l) or even abolished (5 mmol/l) the contractile response of the rat portal vein to angiotensin II, supporting the conclusion that these receptors can be classified as AT₁-receptors.

In conclusion, the receptor subtype mediating the angiotensin II-induced potentiation of the spontaneous phasic contractions in the rat portal vein appears to belong to the AT₁-receptor subtype.