Alpha-2-adrenoceptors are involved in mediation of norepinephrine-induced constriction in rabbit interlobular arteries

• Main Author: Patel, Charvi Ashok
• Format: Dissertation
• Language: English
• Published: ProQuest Dissertations & Theses 01-01-1997
• Subjects: Immunology; Pharmacology
• ISBN: 0591515652; 9780591515657

The presented functional and immunohistochemical studies were designed to test the hypothesis that $\alpha\sb2$-adrenoceptors which mediate vasoconstriction are located in one or both of two previously unexamined sequential intrarenal artery segments of rabbits: arcuate artery (ARC) and interlobular artery (ILUA). We functionally characterized the $\alpha$-adrenoceptor subtypes ($\alpha\sb1$ and/or $\alpha\sb2)$ in NE-induced vasoconstriction in the ARC and ILUA, utilizing a modification of an in vitro method developed by Mulvany and Halpern (1976). The larger diameter ARC exhibited greater contractile sensitivity to exogenous norepinephrine (NE), than the smaller ILUA. Sensitivity to the selective $\alpha\sb1$-adrenoceptor agonist phenylephrine (PE) did not differ in the ARC and the ILUA, but the maximal contractile response of each artery to PE was greater than that to NE. The $\alpha\sb1$-adrenoceptor antagonist prazosin shifted the concentration-response curves to NE rightward in both the ARC and the ILUA. The a$\sb2$-adrenoceptor antagonist yohimbine shifted the concentration-response curves to NE rightward in the ILUA, but had no significant effect in the ARC. Yohimbine had no significant effect on the concentration-response curves to PE in the ILUA. Both clonidine and 5-bromo-6-(2-imidazolin-2-ylamino)-quinoxaline (UK14304), $\alpha\sb2$-adrenoceptor agonists, produced significantly greater contractile responses in the ILUA than in the ARC. Yohimbine shifted the concentration-response curves to UK14304 rightward in the ILUA. Prazosin, the $\alpha\sb1$ antagonist and a purported $\rm\alpha\sb{2B}$ and $\rm\alpha\sb{2C}$ antagonist significantly shifted UK14304 contractile responses to the right in the ILUA. The combination of both prazosin (10$\sp{-7}$ M) and yohimbine (10$\sp{-7}$ M) shifted concentration-response curves to UK14304 rightward in the ILUA. These results suggest that NE-induced vasoconstriction is predominantly mediated by $\alpha\sb1$-adrenoceptors in the larger artery (ARC), but by $\alpha\sb2$-adrenoceptors as well as $\alpha\sb1$-adrenoceptors in the ILUA. We investigated the localization of $\alpha\sb2$-adrenoceptor subtypes in the rabbit ARC and ILUAs of the kidney using a new protocol, allowing specific rabbit antisera to detect rabbit antigens in rabbit renal tissue sections. These $\alpha\sb2$-adrenoceptor subtype specific antibodies were employed to target the receptors. $\rm\alpha\sb{2A}$-like immunoreactivity was detected in the outermost vascular smooth muscle, the adventitia and the perivascular connective tissue, $\rm\alpha\sb{2B}$-like immunoreactivity was found in the endothelium and $\rm\alpha\sb{2C}$-like immunoreactivity was observed in the innermost smooth muscle layer, adventitia and connective tissue and, possibly, the endothelium of the ILUA. In contrast, no $\rm\alpha\sb{2A},\ \alpha\sb{2B}\ or\ \alpha\sb{2C}$-like immunoreactivity was observed in the vascular endothelium or the smooth muscle of the ARC. Some scattered $\rm\alpha\sb{2C}$-like immunoreactivities were observed in the adventitia and the perivascular connective tissue of the ARC. The morphologic observations support our functional data and suggest that $\alpha\sb2$-adrenoceptors are located within the ILUA, but not within the ARC. Furthermore, varying subtypes of $\alpha\sb2$-adrenoceptors are located in different regions of the ILUA.