Impact of alpha1-adrenoceptor expression on contractile properties of vascular smooth muscle cells.
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.
Gericke
Adrian
A
Institute of Vegetative Physiology, Charité University Medicine, Tucholskystr. 2, 10117 Berlin, Germany. adrian.gericke@gmx.net
Martinka
Peter
P
Nazarenko
Irina
I
Persson
Pontus B
PB
Patzak
Andreas
A
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002469:Cell Separation; D005822:Genetic Vectors; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D018613:Microscopy, Confocal; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D014162:Transfection
C547715:Adra1a protein, rat; C547718:Adra1b protein, rat; C547721:Adra1d protein, rat; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D019138:Antibodies, Blocking; D018340:Receptors, Adrenergic, alpha-1; D010656:Phenylephrine