Alteration of volume-regulated chloride movement in rat cerebrovascular smooth muscle cells during hypertension.
The cerebrovascular remodeling is a prominent feature of hypertension and considered a major risk factor for stroke. Cerebrovascular smooth muscle cells meet volume challenge during this pathophysiological process. Our previous studies suggest that volume regulated chloride channels may be critical to the cell cycle of vascular smooth muscle cells. However, it is unknown whether the volume-regulated chloride movement is altered in hypertension. Therefore, we directly measured the concentration of intracellular chloride ([Cl(-)](i)) in rat basilar arterial smooth muscle cells isolated from control rats and rats that were made hypertensive for 1 to 12 weeks after partial renal artery constriction (2-kidney, 2-clip method) using a 6-methoxy-N-ethylquinolinium iodide fluorescence probe. The [Cl(-)](i) in isotonic solution showed no difference in all of the groups. After hypotonic perfusion, the reduction in [Cl(-)](i) was more prominent in hypertensive cerebrovascular smooth muscle cells than in sham control cells. Genistein, a protein tyrosine kinase inhibitor, inhibited hypotonic-induced reduction in [Cl(-)](i), whereas sodium orthovanadate, a protein-tyrosine phosphatase inhibitor, enhanced hypotonic-induced reduction in [Cl(-)](i) in both groups. The percentage inhibition of reduction in [Cl(-)](i) by genistein on volume-regulated chloride movement has a positive correlation with blood pressure levels in the 2-kidney, 2-clip hypertensive group, as is the case for the percentage increase of reduction in [Cl(-)](i) by sodium orthovanadate. Antihypertensive therapy with the angiotensin-converting enzyme inhibitor captopril completely reversed abnormal volume-regulated chloride movement in hypertensive rats. We conclude that volume-regulated chloride movement is augmented in rat cerebrovascular smooth muscle cells in proportion to the severity of hypertension.
Shi
Xiao-Lian
XL
Department of Pharmacology, Zhongshan Medical College, Sun Yat-Sen University, 74 Zhongshan 2 Rd, Guangzhou, 510089, People's Republic of China.
Wang
Guan-Lei
GL
Zhang
Zheng
Z
Liu
Yu-Jie
YJ
Chen
Jing-Hui
JH
Zhou
Jia-Guo
JG
Qiu
Qin-Ying
QY
Guan
Yong-Yuan
YY
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D048429:Cell Size; D002536:Cerebral Arteries / Q000378:metabolism* / Q000473:pathology; D002712:Chlorides / Q000378:metabolism*; D004195:Disease Models, Animal; D019833:Genistein / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D014638:Vanadates / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002712:Chlorides; D014638:Vanadates; D002216:Captopril; D019833:Genistein; D011505:Protein-Tyrosine Kinases