Enhanced vascular reactivity to mastoparan, a g protein activator, in genetically hypertensive rats

Nancy L. Kanagy, R. Clinton Webb

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Vascular smooth muscle from stroke-prone spontaneously hypertensive rats has an increased responsiveness to the vasoconstrictors angiotensin II and serotonin. This abnormality is postulated to contribute to the hypertension characteristic of this strain of rats. We hypothesized that a portion of the increased responsiveness may be due to altered function of G proteins. This hypothesis was tested using mastoparan, a peptide that mimics ligand-bound receptors to stimulate G proteins directly. In addition, we investigated the mechanism of mastoparan-induced contraction of vascular smooth muscle. Changes in isometric tension were recorded in denuded carotid artery strips from hypertensive and normotensive (Wistar-Kyoto) rats. Vascular strips from the hypertensive rats had a significantly greater response to mastoparan at all concentrations between 10−8 and 10−5 mol/L. A G protein inhibitor, N-ethylmaleimide (10−3 mol/L), attenuated the response to mastoparan (10−7 mol/L) (67±4% of control response), whereas pertussis toxin treatment did not. Inhibition of phospholipase C also significantly decreased the mastoparan- induced response (23±12% of control), and nifedipine (10−3 mol/L), a calcium channel blocker, completely blocked the mastoparan-induced contraction. Indomethacin treatment did not affect the mastoparan contraction even though mastoparan has been shown to stimulate phospholipase A2 in other cell types. In conclusion, we observed an increased response in carotid arteries from genetically hypertensive rats to a pharmacological intervention that appears to act via G protein-linked phospholipase C stimulation and L-type calcium channel activation, suggesting that the increased vascular reactivity in stroke-prone spontaneously hypertensive rats is due in part to altered function of G proteins.

Original languageEnglish (US)
Pages (from-to)946-950
Number of pages5
JournalHypertension
Volume23
Issue number6
DOIs
Publication statusPublished - Jun 1994
Externally publishedYes

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Keywords

  • Calcium channels
  • Inbred SHR
  • Muscle
  • Phospholipase C
  • Rats
  • Smooth
  • Vascular

ASJC Scopus subject areas

  • Internal Medicine

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