Tyrosine phosphorylation of paxillin may be involved in vascular smooth muscle contraction

Paxillin is a regulatory component of the complex of cytoskeletal proteins that link the actin cytoskeleton to the plasma membrane. However, the role of paxillin during smooth muscle contraction is unclear. We investigated a possible role for the membrane-associated dense plaque protein paxillin in the regulation of contraction in rat aortic vascular smooth muscle. The tyrosine phosphorylation of paxillin, which was increased by norepinephrine, reached a peak level after 1 min stimulation and then decreased with time. However, norepinephrine induced a sustained contraction that reached a steady state 30 min after application. Pretreatment with tyrphostin, an inhibitor of tyrosine kinase, inhibited the tyrosine phosphorylation of paxillin and also the contraction stimulated by norepinephrine. Both inhibitions were concentration-dependent, and the degree of correlation between them was high. These results show that, in rat aortic smooth muscle, tyrosine kinase(s) activated by norepinephrine may phosphorylate the tyrosine residues of paxillin, thereby providing a source of regulation during vascular smooth muscle contraction.

Role of Tyrosine Kinases in 5-HT-Induced Vascular Contraction in Two-Kidney, One Clip Hypertensive Rats / 대한신장학회잡지

Tyrosine kinases have been implicated in vascular smooth muscle cell proliferation and contraction. The involvement of tyrosine kinases in 5-hydroxytryptamine (5-HT)-induced contractile response of the isolated aorta was examined in two-kidney, one clip (2K1C) hypertensive rats, 2141C hypertension was made by constricting the left renal artery and age-matched control rat received sham treatment. Thoracic aortic rings denuded of endotheliurn were mounted in tissue bath, for measurement of isometric contractile force. The putative tyrosine kinase inhibitor, genistein, shifted concentration-response curves to 5-HT toward the right in control rats The isometric force generation induced by 5-HT was also inhibited by genistein in aortic rings from 2K1C: hypertensivc rats, however genistein did not affect on the high concentration of 5-HT in hypertensive rat ;. Genistein-induced relaxations were more attenuated in aortae from hypertensive rats than those from control Genistein had no effect on contrartcion elicited by the direct protein kinase C activator, phorbol 12, 13 dibutyrate (PDBu) either in 2KlC hypertensive or in control Group. These findings indicate that genistein-sensitive tyrosine kinases paeticipate in 5-HT-induced contraction of rat aortic smooth muscle, of which role is apparent in 2K1C: hypertension.

Role of tyrosine kinases in vascular contraction in deoxycorticosterone acetate-salt hypertensive rats

It has been known that activation of tyrosine kinases is involved in signal transduction. Role of the tyrosine kinase in vascular smooth muscle contraction was examined in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Male Sprague-Dawley rats underwent uninephrectomy, one week after which they were subcutaneously implanted with DOCA (200 mg/kg) and supplied with 1% NaCl and 0.2% KCl drinking water for 4-6 weeks. Control rats were treated the same except for that no DOCA was implanted. Helical strips of carotid arteries were mounted in organ baths for measurement of isometric force development. Genistein was used as a tyrosine kinase inhibitor. Concentration-response curves to 5-hydroxytryptamine (5-HT) shifted to the right by genistein in both DOCA-salt hypertensive and control rats. Although the sensitivity to genistein was similar between the two groups, the maximum force generation by 5-HT was less inhibited by genistein in arteries from DOCA-salt hypertensive rats than in those from controls. Genistein-induced relaxations were attenuated in arteries from DOCA-salt rats. Genistein affected the contraction to phorbol 12, 13-dibutyrate (PDBu) neither in DOCA-salt nor in control arteries. These observations suggest that tyrosine kinase is involved in 5-HT-induced vascular contraction, of which role is reduced in DOCA-salt hypertension.

Effect of Thiopental and Thiamylal on Isolated Thoracic Aorta in Normotensive and Spontaneously Hypertensive Rats / 대한마취과학회지

The present study was undertaken to measure the effects of thiopental and thiamylal on isolated thoracic aortic hlical strips in normotensive Wistar rats(NWR) and spontaneously hypertensive rats(SHR). Phenylphrine(10(-9) ~ 10(-5) M) caused a dose-dependant contraction in thoracic aortic strips contracted with 30mM KCI in NWR and SHR. The contraction induced by 30mM KCI was taken as 100% and the mean absolute values of NWR and SHR were 463+/-30 and 457+/-38mg, respectively. The ED50 of phenylphrine in thoracic aortic strips contracted with 30mM KCI in NWR and SHR was (2.3+/-1.2) X 10(-8) M and (2.1+/-1.1) X 10(-9) M, respectively. There were no significant differences in the contractile response of thoracic aorta from NWR and SHR to 30mM KCI. In helically cut strips of thoracic aorts contracted with 30mM KCI, the cumulative administration of thiopental (10(-5) ~ 10(-3) M) caused a dose related contraction in NWR and SHR. The contraction induced by 30mM KCI was taken as 100% and the mean absolute values of NWR and SHR were 496+/-31 and 541+/-69mg, respectively. There were significant differences (p<0.05 and p<0.01) in the contractile responses of thoracic aorta from NWR and SHR to thiamylal(3X10(-4) and 10(-3) M). The dose-related contraction to thiamylal was greater than that to thiopental in NWR and SHR.