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(Hypertension. 1996;27:740-745.)
© 1996 American Heart Association, Inc.

Articles

Increased Responsiveness and Decreased Expression of G Proteins in Deoxycorticosterone Hypertension

Nancy L. Kanagy; R. Clinton Webb

From the Department of Physiology, University of New Mexico School of Medicine, Albuquerque (N.L.K.); and the Department of Physiology, University of Michigan, Ann Arbor (R.C.W.).

Correspondence to Dr Nancy L. Kanagy, Department of Physiology, 237 Basic Medical Sciences Bldg, University of New Mexico School of Medicine, Albuquerque, NM 87131-5321.

Abstract Deoxycorticosterone-salt (DOCA-salt) hypertension is characterized by elevated vasoconstriction to agonists that stimulate G protein–mediated activation of phospholipase C. However, the mechanisms responsible for the augmented responsiveness are unknown. This study tested the hypothesis that this augmented vascular responsiveness is due to elevated content of G_q, the G protein -subunit that activates phospholipase C. Thoracic aortae from DOCA-salt hypertensive rats (systolic blood pressure 183±7 mm Hg) and normotensive controls (systolic blood pressure 115±2 mm Hg) were homogenized and G protein content determined. Western analysis revealed that G_i content was decreased in DOCA compared with control rats (1364±196 versus 2343±188 densitometry units, P.05) with no differences observed for G_q or G_s. In addition, contractile responses in denuded femoral artery strips revealed a significant decrease in EC₅₀ values in DOCA arteries to all of the agonists examined: aluminum fluoride (DOCA=1.42, control=2.34 mmol/L), mastoparan (DOCA=0.51, control=35 µmol/L), phenylephrine (DOCA=0.08, control=0.53 µmol/L), and serotonin (DOCA=0.014, control=0.04 µmol/L, EC₂₀ values). Finally, arteries from DOCA rats contracted with aluminum fluoride had increased sensitivity to G protein antagonists but not to a phospholipase C inhibitor. The enhanced contractile responsiveness in the DOCA arteries may be mediated in part through decreased G_i levels. However, it is not caused by increased concentrations of G_q in the cell membrane or by increased phospholipase C sensitivity, and the increased constrictor response to G protein stimulators of phospholipase C appears to depend primarily on increased G protein sensitivity.

Key Words: aluminum fluoride • mineralocorticoids • G proteins

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