The alpha2-AR represent a multigene family of membrane proteins which includes at least 3 distinct members (subtypes). It is our hypothesis that alterations in function or expression of the a2-AR in certain areas of brain or kidney may be associated with pathological conditions leading to elevation in blood pressure. Our overall objective is to study the expression of the various alpha2-AR genes in brain and kidney tissues in normotension and hypertension.
The specific aims are as follows: (1) To study the expression of the three alpha2-AR expression in brain and kidney normotensive Wistar-Kyoto (WKY) rats using in situ hybridization with three alpha2-AR probes, which can distinguish transcripts from the three different rat alpha2-AR genes. (2) To study alpha2-AR expression in brain and kidney of different hypertensive rat models: the genetically spontaneously hypertensive rat (SHR), the subtotally nephrectomized Wistar with acquired salt-induced hypertension and the renovascular two- kidney, one-clip model during the renin and non-renin dependent phases (Wistar). Each group will be compared with the appropriate normotensive controls. (a) RNase protection and in situ hybridization will be used to analyze transcript expression; whereas, (b) radioligand binding and GTPase assays will be investigate whether alpha2-AR expression is altered by lowering blood pressure in SHR or WKY by administration of the following treatments: and alpha2- agonist; a tyrosine hydrolase inhibitor together with reserpine; and a non-specific vasodilator. These studies will clarify whether any observed of the hypertensive state. RNase protection will be used to compare levels of transcripts in treated and untreated rats. These studies should provide new information regarding the participation of alpha2-AR subtypes in genetic or acquired salt- dependent hypertension and the relationship of alpha2-AR differences to the hypertensive state per se.
| Gavras, I; Gavras, H (2001) Role of alpha2-adrenergic receptors in hypertension. Am J Hypertens 14:171S-177S |
| Gavras, I; Manolis, A J; Gavras, H (2001) The alpha2 -adrenergic receptors in hypertension and heart failure: experimental and clinical studies. J Hypertens 19:2115-24 |
