Chlopicki S, Kozlovski V I, Gryglewski R J
Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland.
J Physiol Pharmacol. 2003 Dec;54(4):511-21.
Functional role of endothelial alpha(2)-adrenoceptor in coronary circulation remains unclear. Clonidine, an agonist of alpha(2)-adrenoceptors, was reported to induce coronary vasodilatation via stimulation of endothelial alpha(2)-adrenoceptors or coronary vasoconstriction involving vascular smooth muscle alpha(2)-adrenoceptors. Moreover, H(2) receptor-dependent responses to clonidine were described. Here, we reassess the contribution of endothelial alpha(2)-adrenoceptor and H(2) receptors to coronary flow and contractility responses induced by clonidine in the isolated guinea pig heart. We found that clonidine (10(-9) - 10(-6) M) produced concentration-dependent coronary vasoconstriction without a significant change in contractility. This response was inhibited by the alpha(1)/alpha(2)-adrenoceptor antagonist - phentolamine (10(-5) M) and the selective alpha(2)-adrenoceptor antagonist yohimbine (10(-6) M), but it was not changed by the selective alpha(1)-adrenoceptor antagonist prazosin (10(-6) M). In the presence of nitric oxide synthase inhibitor, L-NAME (10(-4) M) the clonidine-induced vasoconstriction was potentiated. Clonidine at high concentrations of 10(-5) - 3 x 10(-5) M produced coronary vasodilatation, and an increase in myocardial contractility. These responses were abolished by a selective H(2)-receptor antagonist, ranitidine (10(-5) M), but not by phentolamine (10(-5) M). We conclude that in the isolated guinea pig heart, clonidine-induced vasoconstriction is mediated by activation of smooth muscle alpha(2)-adrenoceptors whereas clonidine-induced coronary vasodilatation is mediated by activation of vascular H(2) histaminergic receptors. Accordingly, endothelial alpha(2)-adrenoceptors does not seem to play a major role in coronary flow response induced by clonidine.
内皮α₂ - 肾上腺素能受体在冠脉循环中的功能作用仍不清楚。据报道，α₂ - 肾上腺素能受体激动剂可乐定可通过刺激内皮α₂ - 肾上腺素能受体诱导冠脉血管舒张，或通过涉及血管平滑肌α₂ - 肾上腺素能受体诱导冠脉血管收缩。此外，还描述了对可乐定的H₂受体依赖性反应。在此，我们重新评估内皮α₂ - 肾上腺素能受体和H₂受体对可乐定在离体豚鼠心脏中诱导的冠脉血流和收缩反应的作用。我们发现，可乐定（10⁻⁹ - 10⁻⁶ M）产生浓度依赖性的冠脉血管收缩，而收缩性无显著变化。该反应被α₁/α₂ - 肾上腺素能受体拮抗剂酚妥拉明（10⁻⁵ M）和选择性α₂ - 肾上腺素能受体拮抗剂育亨宾（10⁻⁶ M）抑制，但不受选择性α₁ - 肾上腺素能受体拮抗剂哌唑嗪（10⁻⁶ M）影响。在一氧化氮合酶抑制剂L - 精氨酸甲酯（L - NAME，10⁻⁴ M）存在的情况下，可乐定诱导的血管收缩增强。高浓度（10⁻⁵ - 3×10⁻⁵ M）的可乐定产生冠脉血管舒张，并增加心肌收缩性。这些反应被选择性H₂受体拮抗剂雷尼替丁（10⁻⁵ M）消除，但不被酚妥拉明（10⁻⁵ M）消除。我们得出结论，在离体豚鼠心脏中，可乐定诱导的血管收缩是由平滑肌α₂ - 肾上腺素能受体的激活介导的，而可乐定诱导的冠脉血管舒张是由血管H₂组胺能受体的激活介导的。因此，内皮α₂ - 肾上腺素能受体似乎在可乐定诱导的冠脉血流反应中不发挥主要作用。
