Increased responsiveness and decreased expression of G proteins in deoxycorticosterone hypertension

Nancy L. Kanagy, R. Clinton Webb

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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 Gα(q), the G protein α-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 Gα(i) content was decreased in DOCA compared with control rats (1364 ± 196 versus 2343 ± 188 densitometry units, P ≤ .05) with no differences observed for Gα(q) or Gα(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 Gα(i) levels. However, it is not caused by increased concentrations of Gα(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.

Original languageEnglish (US)
Pages (from-to)740-745
Number of pages6
JournalHypertension
Volume27
Issue number3 II
StatePublished - Mar 1 1996
Externally publishedYes

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Keywords

  • G proteins
  • aluminum fluoride
  • mineralocorticoids

ASJC Scopus subject areas

  • Internal Medicine

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