Influence of losartan and nicardipine on the contractile responses of human subcutaneous arteries and veins to angiotensin II

In the human forearm vascular bed, the arterial constrictor effects of angi otensin II were found to be caused by an AT(1)-receptor mediated calcium in flux, while the venous constrictor effects appeared to be independent of L- type calcium channels. In this study, we investigated the influences of the AT(1)-receptor antagonist losartan and the calcium channel blocker nicardi pine on the angiotensin II-induced constriction of small isolated subcutane ous arteries and veins obtained from human mammary tissue. Subcutaneous art eries and veins were isolated from mammary tissue from 9 healthy women who underwent breast reduction surgery. Effects of angiotensin II (0.3 nM to 1 mM), losartan (0.1 mM) and nicardipine (0.1 mM) were investigated in a myog raph set up. Identification of arteries and veins was confirmed histologica lly after the experiments. Drug effects were expressed relatively to the po tassium-induced contraction. Angiotensin II concentration-dependently contr acted arteries and veins by maximally 1.66 +/- 0.31 N/m and 0.43 +/- 0.08 N /m, respectively (P < 0.05). In arteries the angiotensin II were subject to a mild degree of tachyphylaxis: the E-max of the repetitive concentration- response curve (CRC) was reduced from 105 +/- 4% of the potassium-induced c ontraction to 84 +/- 6% (P < 0.05); the EC50 value was unchanged (P > 0.05) . In veins no tachyphylaxis was observed. Losartan caused a rightward shift of the CRC of angiotensin II in arteries and veins (P < 0.05), and reduced the E-max in arteries from 105 +/- 4 to 85 +/- 9% (P < 0.05), but did not change the E-max in veins. Nicardipine significantly decreased the E-max in arteries and veins (to residual values of 10 +/- 2 and 20 +/- 4%, respecti vely, of the control values). In conclusion, the angiotensin II-induced con striction of human arteries and veins isolated from mammary tissue are AT(1 )-receptor mediated and inhibited by losartan. The nearly complete inhibiti on by nicardipine indicates that the constrictor effects in both types of v essels are dependent on L-type calcium channels. (C) Elsevier, Paris.