Enhanced activation of RhoA by angiotensin II in SHR preglomerular microvascular smooth muscle cells.
Angiotensin II causes a greater renal vasoconstriction in spontaneously hypertensive rats (SHR) than in normotensive Wistar Kyoto rats (WKY), and alpha2-adrenoceptor agonists potentiate angiotensin II-induced renal vasoconstriction more in SHR. Because angiotensin II activates RhoA, and RhoA contributes to vasoconstriction, we tested the hypothesis that the ability of angiotensin II to stimulate RhoA in preglomerular vascular smooth muscle cells and the ability of alpha2-adrenoceptor activation to potentiate this response are augmented in cells from SHR. In SHR preglomerular vascular smooth muscle cells, angiotensin II (1 micromol/L) greatly stimulated RhoA activity, and this effect was markedly potentiated by UK 14,304 (1 micromol/L; alpha2-adrenoceptor agonist) (fold increase from vehicle-treated cells: 9.0 +/- 2, 0.8 +/- 0.2, and 13.6 +/- 3.2 in cells treated with angiotensin II, UK 14,304, and angiotensin II + UK 14,304, respectively). In contrast, in WKY cells, angiotensin II only mildly activated RhoA (2.0 +/- 0.50), and this response was not enhanced by UK 14,304. The expression of Galpha12 and Galpha13, G-proteins thought to link G-protein-coupled receptors to RhoA, was not increased in SHR cells. We conclude that angiotensin II-induced activation of RhoA is much more robust in the preglomerular microcirculation of SHR compared with WKY and that this may contribute to the etiology of genetic hypertension.
Jackson
Edwin K
EK
Center for Clinical Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA. edj+@pitt.edu
Andresen
Bradley T
BT
Seasholtz
Tammy M
TM
Zhu
Chongxue
C
Romero
Guillermo G
GG
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D006973:Hypertension / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000098:blood supply* / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008833:Microcirculation / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D000804:Angiotensin II; D020742:rhoA GTP-Binding Protein