ABSTRACT
alpha-Adrenoceptor agonists and antagonists are widely used perioperatively for internal mammary artery (IMA)-coronary artery bypass operations. To determine subtypes of alpha-adrenoceptors in the human IMA, we studied responses of isolated human IMA segments to alpha-adrenoceptor agonists, antagonists, and electrical stimulation in organ baths. The IMA ring segments (3 mm long) were set up at a physiologic and comparable condition according to their own length-tension curves. alpha 1-Agonist methoxamine (MO) induced 2.65 +/- 0.70 g force and alpha 1, alpha 2-agonist norepinephrine (NE) induced 4.07 +/- 0.70 g force. The contractions induced by both MO and NE were totally abolished by alpha 1-antagonist prazosin (0.1 microM) but not alpha 2-antagonist yohimbine. alpha 2-Agonist UK14304 induced only 0.39 +/- 0.17 g force, which was significantly less than that induced by MO or NE (p < 0.001). Contractions induced by electrical field stimulation (2, 10, 20 Hz) were decreased by alpha 1-antagonist prazosin 1 microM (p < 0.01) but potentiated by alpha 2-antagonist yohimbine. These results strongly suggest that in the human IMA the postjunctional alpha-adrenoceptors are predominantly of the alpha 1-subtype and therefore the alpha-adrenoceptor agonist-induced contraction and the sympathetic nerve stimulation-induced contraction is mediated mainly by activation of the alpha 1-adrenoceptors.
Subject(s)
Muscle, Smooth, Vascular/physiology , Receptors, Adrenergic, alpha/physiology , Adrenergic alpha-Agonists/pharmacology , Adrenergic alpha-Antagonists/pharmacology , Electric Stimulation , Female , Humans , In Vitro Techniques , Male , Mammary Arteries/drug effects , Mammary Arteries/physiology , Middle Aged , Muscle Contraction/drug effects , Muscle, Smooth, Vascular/drug effects , Receptors, Adrenergic, alpha/drug effects , Sympathetic Nervous System/drug effects , Sympathetic Nervous System/physiologyABSTRACT
1. Sympathomimetic amines have been considered to be related to vasospasm. Previous studies showed that the human internal mammary artery (IMA) was capable of weak beta-adrenoceptor mediated relaxation and that alpha-adrenoceptor agonists may induce contraction in the human IMA. 2. We investigated the effects of glyceryl trinitrate (GTN), a vasodilator agent often used perioperatively, on alpha-adrenoceptor mediated contraction in the human IMA. 3. Discarded human IMA segments were taken from 37 patients who underwent IMA--coronary artery bypass graft operations and equilibrated in an organ bath. 4. A specially designed technique was used to normalize the vessel segments under the pressure similar to the in vivo situation. Noradrenaline (NA), phenylephrine (PE), and methoxamine (MO) were used to contract the vessel segments. 5. GTN fully relaxed PE or MO (submaximal concentration) induced precontraction. Therapeutic plasma concentration of GTN relaxed 40-90% of the PE induced contraction (2.82 g, EC50 = 7.92 +/- 0.06 -log M) and 20-90% of the MO induced contraction (1.8 g, EC50 = 7.63 +/- 0.16 -log M). Pretreatment by the therapeutic plasma concentration of GTN inhibited the contraction induced by NA, PE in a different range. It reduced the NA induced contraction (6.9 g) by 14.8-38% (P greater than 0.05) and the PE induced contraction (4.3 g) by 7.9-39.3% (P greater than 0.05). The alpha 1-adrenoceptor antagonist prazosin, at the therapeutic plasma concentration, nearly totally abolished the NA or PE induced contraction (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
