Role of Alpha-1 Adrenoceptor Subtypes Mediating Constriction of the Rabbit Ear Thermoregulatory Microvasculature

Abstract

Summary: An acute in vivo preparation of the microvasculature of the rabbit ear was used to evaluate the functional role of alpha, (al)-adrenoceptor subtypes in thermoregulatory microcirculation. The effect of al-adrenoceptor subtype blockade on phenylephrine-induced vasoconstriction was assessed with the alA, alB, and alD-adrenoceptor-selective antagonists 5-methyl-urapidil M ) . chloroethylclonidine (1 0-j M ) , and X-[2-[4(2-methoxyphenyl)-l-piperazinyl]ethyl]-8-azaspirol[4.S]decane-7,9-dione dihydrochloride (BMY7378) (10-6 M ) , respectively. The results demonstrated that pretreatment of the ear microvasculature with 5-methylurapidil or BMY7378 shifted the phenylephrine concentration-response curve rightward and significantly changed the log of the phenylephrine concentration, causing half-maximum stimulation (EC,,) in arterioles (p < 0.05). BMY7378 shifted the phenylephrinc concentration-response curve of the arteriovenous anastomoses about 100-fold rightward (p < 0.05). All three a,-adrenoceptor antagonists eliminated the vasoconstrictive effects of phenylephrine on venules. The results indicate that the ear microvasculature has a heterogenous distribution of ul-adrenoceptor subtypes. The alA and alD-adrenoceptor subtypes appear to have a greater influence on constrictive function in arterioles, whereas the alD-adrenoceptor is the dominant constrictor of arteriovenous anastomoses. In general, the al-adrenoceptor does not play a major vasoconstrictor role in venules. Chloroethylclonidine, an irreversible alB-adrenoceptor antagonist, induced contractile responses in the ear microvasculature, probably due to its a2-adrenoceptor agonist effects. This study extended our understanding of the adrenergic receptor control mechanisms of a cutaneous thermoregulatory end organ characterized by two parallel perfusion circuits providing nutritional and thermoregulatory functions.The microvasculature of the rabbit ear, like that of the human digit, consists of terminal arterioles, capillary loops, postcapillary venules, and arteriovenous anastomoses. The arteriovenous anastomoses allow blood to bypass the capillaries to flow directly into the deep venous plexus and are believed to be involved in thermoregulation (5). Skin blood vessels affect homeostasis of body temperature by dilating in response to heating and constricting in response to cooling. Changes in tonic sympathetic outflow are largely responsible for control of these vessels. The vasoconstrictor responses induced by exogenous norepinephrine, norepinephrine-like compounds, or sympathetic activation are mediated by alpha, (a1) and a,-adrenoceptors. Previous studies in our laboratory demonstrated that the resistance arterioles and arteriovenous anastomoses have different adrenoceptor control mechanisms (9,16): a,-adrenoceptors dominate arteriolar constriction, whereas the arteriovenous anastomoses are dually regulated by a, and a2-adrenoceptors (9,16). These findings provide a possible explanation of how blood flow in the ear is distributed between two parallel ...

Functional subtypes of renal α1-adrenoceptor in diabetic and non-diabetic 2K1C Goldblatt renovascular hypertension

“…It can also be suggested that in these rats, there could be an upregulation of α 1Aadrenoceptors or involvement of presynaptic α 1Badrenoceptors in determining renal vasoconstriction. In the later case, it can be suggested that when these receptors are blocked by chloroethylclonidine, the presynaptic auto-inhibitory feedback is removed and allows more NA to be released, which consequently results in a larger post-synaptic response [37] . Another possible explanation of these observations could be the downregulation of certain α 1adrenoceptors in the renal vasculature.…”

The contribution of adrenoceptor subtype(s) in the renal vasculature of diabetic spontaneously hypertensive rats

“…These authors observed that in the kidneys of NA-treated rats, the enhanced fractional neurotransmitter release that led to vasoconstriction, was a consequence of a reduction in prejunctional a-adrenoceptors. Other possible explanations might be an upregulation of a 1A , or an involvement of either presynaptic a 1B or a 2 -adrenoceptors in determining renal vasoconstriction which, when blocked, removed the presynaptic autoinhibitory feedback, allowing more NA release and a larger postsynaptic response (Li et al, 2000).…”