Changes in α2-Adrenoceptors on Vascular Smooth Muscle and Neural Membranes following Hypertension Induced by Renal Ischemia

Abstract

α₂-Adrenoceptors were characterized on neural and vascular membranes from 2-kidney-1-clip renal hypertensive (RHT) and normotensive (NT) rats. Rats were sacrificed 6 weeks after induction of renal ischemia, and the specific binding of ³H-clonidine to smooth muscle membranes from tail arteries and neural membranes from various brain regions was examined. Additionally, isometric contractions of helically cut tail artery strips produced by various α-adrenoceptor agonists were measured. Scatchard analysis indicated an increased number of high-affinity binding sites on the smooth muscle membranes from RHT rats (Bmax = 43.5 ± 1.4 fmol/mg protein) compared to that from the NT rats (25.4 ± 3.8 fmol/mg protein). An increased contractile sensitivity to clonidine was also observed in tail artery strips from RHT rats (EC₅₀ for RHT = 3.04 x 10^–8M; NT = 1.52 x 10^–7M). In neural tissue, the number of α₂-adrenoceptor-binding sites was significantly increased in the locus coeruleus from RHT rats, but not in the amygdala, hypothalamus, parietal cortex, hippocampus or lower brain stem. These results demonstrate that renal ischemia produces changes in both peripheral and neural α₂-adrenoceptor density. The increase in smooth muscle α₂-adrenoceptors might also provide a partial explanation for the supersensitivity to adrenergic agonists in this model of hypertension.

Differences in α 2 -adrenoceptor modulation of calcium channels in vascular smooth muscle cells of male and female rats

“…In the vascular system, higher levels of α 2 -adrenergic responses appear to be associated with hypertension (e.g. [8]). Reduction of digital blood flow in response to the α 2 -adrenergic agonist clonidine is normally greater in men than in women [3]; however, in Raynaud's disease, in which digital vasospastic attacks occur mainly in women, clonidine sensitivity increases and digital vasospastic attacks can be significantly reduced by α 2 -but not α 1 -adrenergic antagonists [2].…”

“…Alpha-2 adrenergic receptors are found in blood vessels both on endothelial cells, where they stimulate release of endothelium-derived relaxing factor [5], and on smooth muscle cells (VSMC), where they stimulate contraction [8]. We focus here on the α 2 -adrenergic response of VSMC isolated from blood vessels, thereby studying VSMC responses independent of the influence of endothelial cell-mediated mechanisms.…”