To the Editor:—

I read with interest the study about the effect of α-2 adrenergic agonists on the spinal pial microcirculation in dogs. 1Using an in vivo  technique, the authors observed a significant constriction of both pial arterioles and venules after topical application of clonidine or dexmedetomidine. They suggested that α-2 agonists might be superior to epinephrine or phenylephrine as local anesthetics additives since the latter induced a greater constriction of pial microvessels and therefore may jeopardize spinal blood flow. It has been known that α-2 adrenoceptors are present on both vascular smooth muscles and endothelial cells. The stimulation of α-2 adrenoceptors on vascular smooth muscles is associated with constriction in most vascular beds, whereas activation of endothelial α-2 adrenoceptors relaxes the vascular smooth muscle through a release of endothelium-derived nitric oxide. Distribution of α-2 adrenoceptors may be heterogeneous in various vascular beds. While α-2 adrenergic stimulation induces constriction of canine pial 1and rat intestinal arterioles, 2vasodilation predominates in response to clonidine in the porcine coronary 3and rat coronary 4and uterine 5microcirculation in which nitric oxide plays an important role in the regulation of regional blood flow. Thus, net effect of vascular α-2 adrenergic stimulation is determined by basal α-2 adrenergic activity in the vascular smooth muscle and endothelium. In addition, alterations in endothelial function and structure may affect endothelium-dependent α-2-adrenoceptor-mediated relaxation because of changes in the signal transduction of α-2 adrenergic pathway and production of nitric oxide. Previous study has shown that endothelial injury increases constriction of coronary arterioles to clonidine in septic rats. 4An increase in relaxation response to clonidine is observed in uterine arterioles of pregnant rats, 5likely caused by increased release of nitric oxide. However, no prior study has determined the effect of activation of endothelial α-2 adrenoceptors on vascular reactivity of the spinal microcirculation under different physiologic and pathophysiologic states (e.g. , pregnancy and arteriosclerosis). It is plausible that changes in the endothelium-dependent α-2 adrenoceptor-mediated relaxation of pial microvessels may alter vasoconstrictive effect of α-2 agonists and even duration of spinal anesthesia. Therefore, the conclusion about effectiveness of α-2 adrenergic agonists as local anesthetics additives needs to be reached from the experiment in which the contribution of endothelial α-2 adrenoceptors is determined.

Iida H, Ohata H, Iida M, Watanabe Y, Dohi S: Direct effects of alpha-1 and alpha-2 adrenergic agonist on spinal and cerebral pial vessels in dogs. A nesthesiology 1999; 91:479–85
Cameron EM, Wang SY, Fink MP, Sellke FW: Mesenteric and skeletal muscle microvascular responsiveness in subacute sepsis. Shock 1998; 9:184–92
Wang SY, Friedman M, Johnson RG, Weintraub RM, Sellke FW: Adrenergic regulation of coronary microcirculation after extracorporeal circulation and crystalloid cardioplegia. Am J Physiol 1994; 67:H2462–H2470
Wang SY, Cameron EM, Fink MP, Sellke FW: Chronic septicemia alters alpha adrenergic mechanisms in the coronary circulation. J Surg Res 1997; 69:61–6
Wang SY, Segal S, Thomas JA, Datta S: Pregnancy alters adrenergic mechanisms in the uterine microcirculation in rats. A nesthesiology 1998(suppl): A4