POTENTIATION BY VASOPRESSIN OF ADRENERGIC VASOCONSTRICTION IN THE RATISOLATED MESENTERIC-ARTERY

1. The aim of the present study was to investigate in rat mesenteric a rtery rings whether low concentrations of vasopressin could modify the contractile responses to noradrenaline and electrical stimulation of perivascular nerves. 2. Vasopressin (10(-10)-10(-7) M) caused concentr ation-dependent contractions (pD(2)=8.36+/-0.09). The V-1-receptor ant agonist d(CH2)(5)Tyr(Me)AVP (10(-9)-10(-8) M) produced parallel rightw ard shifts of the control curve for vasopressin. Schild analysis yield ed a pA(2) value of 9.83 with a slope of 1.10+/-0.14.3. Vasopressin (3 x10(-10) and 10(-9) M) caused concentration-dependent potentiation of the contractions elicited by electrical stimulation (2-8 Hz; 0.2 ms du ration for 30 s) and produced leftward shifts of the concentration-res ponse curve for noradrenaline. The V-1-receptor antagonist induced con centration-dependent inhibitions of potentiation induced by vasopressi n. The selective V-1-receptor agonist [Phe(2), Orn(8)]-vasotocin (3x10 (-10) and 10(-9) M) induced potentiation of electrical stimulation-evo ked responses which was also inhibited in the presence of the V-1 anta gonist (10(-8) M). In contrast, the V-2-receptor agonist deamino-8-D-a rginine vasopressin (desmopressin 10(-8)-10(-7) M) did not modify the electrical stimulation-induced responses and the V-2-receptor antagoni st [d(CH2)(5), D-Ile(2), Ile(4), Arg(8)]-vasopressin (10(-8)-10(-7) M) did not affect the potentiation evoked by vasopressin. 4. In artery r ings contracted by 10(-6) M noradrenaline in the presence of 10(-6) M guanethidine and 10(-6) M atropine, electrical stimulation (2, 4 and 8 Hz) produced frequency-dependent relaxations which were unaffected by 10(-9) M vasopressin but abolished by 10(-6) M tetrodotoxin. 5. Vasop ressin also potentiated contractions elicited by KC1 and contractions induced by addition of CaCl2 to KC1 depolarized vessels. The augmentin g effects were inhibited by the V-1 antagonist. 6. In the presence of the calcium antagonist nifedipine (10(-6) M), vasopressin failed to en hance the contractile responses to electrical stimulation, noradrenali ne and KC1. 7. The results demonstrate that low concentrations of vaso pressin strongly potentiate the contractions to adrenergic stimulation and KC1 depolarization. This effect appears to be mediated by V-1 rec eptor stimulation which brings about an increase in calcium entry thro ugh dihydropyridine-sensitive calcium channels.