Effects of calcium- and ETA-receptor antagonists on endothelin-induced vasoconstriction and levels of endothelin in the human internal mammary artery.

1. The effects of the ETA receptor antagonist BQ123 and dihydropyridine calcium antagonists on the vasoconstrictor effect of endothelin-1 (ET-1) were studied in human isolated internal mammary artery (IMA). The effect of the calcium antagonist, nisoldipine, on ET-1 levels has also been examined in cultured IMA endothelial cells (IMAEC). 2. The results showed that BQ123 and the calcium antagonists nisoldipine, isradipine, nitrendipine and nifedipine fully relaxed IMA precontracted with 3 nmol/L ET-1 with the EC50 values of 7.18 +/- 0.09 (-log mol/L) for BQ123, and 7.68 +/- 0.07, 7.02 +/- 0.12, 6.96 +/- 0.08 and 6.89 +/- 0.09 for the calcium antagonists, respectively. 3. Pretreatment of IMA with 10, 30, 100 and 300 nmol/L nisoldipine significantly depressed the maximal response (Max; 88.3 +/- 5.1, 75.2 +/- 4.9, 59.3 +/- 5.6 and 56.2 +/- 4.8% of maximal noradrenaline response versus 99.1 +/- 13.2% in control, P < 0.01) of IMA to ET-1 without a significant change in the EC50 values. 4. Pretreatment of IMA with 300 nmol/L BQ123 significantly increased both the EC50 (7.97 +/- 0.09 vs 8.36 +/- 0.08 in the control, P < 0.05) and the Max (138.1 +/- 10.2% vs the control, P < 0.01) of IMA to ET-1. 5. Incubation of IMAEC with nisoldipine for 7 h resulted in a dose-dependent (10(-8)-10(-5) mol/L) reduction up to 93.1% in ET levels in the conditioned media.(ABSTRACT TRUNCATED AT 250 WORDS)