Contraction of vascular smooth muscle induced by phorbol 12,13 dibutyrate in human and rat pulmonary arteries.

摘要

1. The effect of phorbol 12,13 dibutyrate (PDB) on vascular tone was studied in both human and rat isolated pulmonary arterial strips (HPA and RPA, respectively). 2. PDB (1 nM to 2 microM) produced slowly developing, sustained and concentration-dependent contractions in HPA (mean EC50 = 3.5 nM, n = 5) and RPA (mean EC50 = 120 nM, n = 5). The maximal response was 185.6 +/- 25% and 207 +/- 27.5% (n = 5) of that induced by K(+)-rich (80mM) solution, and 223 +/- 34.5% and 176.5 +/- 38.6% of the noradrenaline (10 microM)-induced contraction in HPA and RPA, respectively. 3. PDB-induced contractions were not altered either by the presence of atropine (10 microM), propranolol (5 microM), phentolamine (5 microM) or tetrodotoxin (10 microM) in the bathing solution, or by the removal of endothelium from pulmonary arteries. 4. In HPA, the amplitude of PDB-induced contractions was significantly reduced by removal of external calcium ions, addition of verapamil (10 microM) or trifluoperazine (TFP, 5 microM) and significantly increased by Bay K 8644 (0.5 microM). In contrast, in RPA, calcium-free solution and verapamil had only a moderate effect on the maximal PDB-induced contraction (approximately 20% reduction), whereas Bay K 8644 and TFP had no significant effect. In both HPA and RPA, PDB-contractions in calcium-free solutions were not modified by ryanodine (25 microM) or by 8-(N,N diethylamino)octyl-3,4,5, trimethoxybenzoate hydrochloride (TMB-8, 50 microM). 5. PDB-induced contractions were inhibited by protein kinase C (PKC) antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)