• Media type: E-Article
  • Title: Influence of losartan and nicardipine on the contractile responses of human subcutaneous arteries and veins to angiotensin II
  • Contributor: Baan, Jan; Pfaffendorf, Martin; van der Wal, Allard C.; Chang, Peter C.; van Zwieten, Pieter A.
  • Published: Wiley, 1999
  • Published in: Fundamental & Clinical Pharmacology, 13 (1999) 1, Seite 43-49
  • Language: English
  • DOI: 10.1111/j.1472-8206.1999.tb00319.x
  • ISSN: 0767-3981; 1472-8206
  • Origination:
  • Footnote:
  • Description: Abstract— 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.