Impact of α₁-adrenoceptor expression on contractile properties of vascular smooth muscle cells

Abstract

Low-frequency blood pressure oscillations (Mayer waves) are discussed as a marker for sympathetic modulation of vascular tone. However, the factors that determine the frequency response of the vasculature to sympathetic stimuli are not fully understood. Possible mechanisms include functions related to alpha(1)-adrenergic receptors (alpha(1)-AR) and postreceptor processes involved in the vascular contractile response. The purpose of the present study was to examine the hypothesis that expression levels of alpha(1)-AR and their subtype distribution determine velocity and magnitude of alpha(1)-AR-mediated vascular smooth muscle cell (VSMC) contraction. alpha(1A)-, alpha(1B)-, and alpha(1D)-AR subtypes were transfected into VSMCs from rat aorta and characterized immunocytochemically via confocal microscopy. Functional studies in isolated cells were performed using video microscopy. The alpha(1)-AR agonist phenylephrine produced dose-dependent contractions of VSMCs. All transfected groups were more sensitive to phenylephrine compared with controls. Maximal contraction velocity almost doubled in transfected cells. However, no differences in observed parameters were found between the three transfected groups. Contractile properties in response to membrane depolarization with KCl were similar in all groups. In conclusion, alpha(1)-AR density determines velocity and sensitivity of alpha(1)-AR-mediated contraction in VSMCs. alpha(1)-AR subtype distribution does not appear to influence vasoconstriction to sympathetic stimuli.

Alterations in sympathetic neuroeffector transmission to mesenteric arteries but not veins in DOCA-salt hypertension

“…Norepinephrine (NE) and ATP are vasoconstrictor transmitters released by perivascular sympathetic nerves (Gitterman and Evans, 2001; Sneddon, 2000). NE acts at α 1 -adrenergic receptors (α 1 -ARs) and ATP acts at P2X and P2Y receptors to cause vasoconstriction (Galligan et al, 2001; Gericke et al, 2007; Gitterman and Evans, 2001; Martínez-Salas et al, 2007; Sneddon, 2000). As MA and MV perform different hemodynamic functions it might be anticipated that different populations of sympathetic neurons would supply MA and MV.…”

Activation of CB1receptors by 2-arachidonoylglycerol attenuates vasoconstriction induced by U46619 and angiotensin II in human and rat pulmonary arteries

“…Pulmonary arterial hypertension (PAH) is a chronic and severe disease of the pulmonary vasculature, which remains incurable thus far. The etiology of PAH involves molecular mechanisms of endothelium dysfunction, leading to an inhibition of the release of vasodilators, along with the simultaneous overexpression of vasoconstrictors, such as thromboxane A 2 (TXA 2 ), angiotensin II (ANG II), serotonin (5-HT), and catecholamines (1,8,28), acting via the G q/11 protein-coupled receptors thromboxane receptor (TP), ANG II receptor type 1 (AT 1 ; 37), 5-HT 2 receptor (12), and ␣ 1 -adrenergic receptor (11,16), respectively.…”

Mechanisms of systemic vasodilation by lysozyme-c in septic shock

“…Cell length was measured with a microscope (Olympus IX 71) attached to a computer with imaging software (In-Vivo and Image-Pro Analyzer, version 6.2; Media Cybernetics, Silver Springs, MD). After baseline lengths of 10 cells were measured, KCl was added to the medium to increase the final concentration to 100 mmol/l to cause the cells to shorten (9). The lengths of the same cells were again measured after 30 min of KCl incubation and after the interventions described below.…”