TY - JOUR
T1 - Influence of losartan and nicardipine on the contractile responses of human subcutaneous arteries and veins to angiotensin II
AU - Baan, J.
AU - Pfaffendorf, M.
AU - van der Wal, A. C.
AU - Chang, P. C.
AU - van Zwieten, P. A.
PY - 1999
Y1 - 1999
N2 - In the human forearm vascular bed, the arterial constrictor effects of angiotensin II were found to be caused by an AT1-receptor mediated calcium influx, while the venous constrictor effects appeared to be independent of L-type calcium channels. In this study, we investigated the influences of the AT1-receptor antagonist losartan and the calcium channel blocker nicardipine on the angiotensin II-induced constriction of small isolated subcutaneous arteries and veins obtained from human mammary tissue. Subcutaneous arteries 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 myograph set up. Identification of arteries and veins was confirmed histologically after the experiments. Drug effects were expressed relatively to the potassium-induced contraction. Angiotensin II concentration-dependently contracted 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 Emax of the repetitive concentration-response curve (CRC) was reduced from 105 +/- 4% of the potassium-induced contraction 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 Emax in arteries from 105 +/- 4 to 85 +/- 9% (P <0.05), but did not change the Emax in veins. Nicardipine significantly decreased the Emax in arteries and veins (to residual values of 10 +/- 2 and 20 +/- 4%, respectively, of the control values). In conclusion, the angiotensin II-induced constriction of human arteries and veins isolated from mammary tissue are AT1-receptor mediated and inhibited by losartan. The nearly complete inhibition by nicardipine indicates that the constrictor effects in both types of vessels are dependent on L-type calcium channels
AB - In the human forearm vascular bed, the arterial constrictor effects of angiotensin II were found to be caused by an AT1-receptor mediated calcium influx, while the venous constrictor effects appeared to be independent of L-type calcium channels. In this study, we investigated the influences of the AT1-receptor antagonist losartan and the calcium channel blocker nicardipine on the angiotensin II-induced constriction of small isolated subcutaneous arteries and veins obtained from human mammary tissue. Subcutaneous arteries 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 myograph set up. Identification of arteries and veins was confirmed histologically after the experiments. Drug effects were expressed relatively to the potassium-induced contraction. Angiotensin II concentration-dependently contracted 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 Emax of the repetitive concentration-response curve (CRC) was reduced from 105 +/- 4% of the potassium-induced contraction 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 Emax in arteries from 105 +/- 4 to 85 +/- 9% (P <0.05), but did not change the Emax in veins. Nicardipine significantly decreased the Emax in arteries and veins (to residual values of 10 +/- 2 and 20 +/- 4%, respectively, of the control values). In conclusion, the angiotensin II-induced constriction of human arteries and veins isolated from mammary tissue are AT1-receptor mediated and inhibited by losartan. The nearly complete inhibition by nicardipine indicates that the constrictor effects in both types of vessels are dependent on L-type calcium channels
U2 - https://doi.org/10.1111/j.1472-8206.1999.tb00319.x
DO - https://doi.org/10.1111/j.1472-8206.1999.tb00319.x
M3 - Article
C2 - 10027087
SN - 0767-3981
VL - 13
SP - 43
EP - 49
JO - Fundamental & clinical pharmacology
JF - Fundamental & clinical pharmacology
IS - 1
ER -