Enhanced vascular reactivity to protein kinase C activators in genetically hypertensive rats

Mlla B. Turla, R. Clinton Webb

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Abstract

Recent studies suggest that phospholipid-sensitive, Ca<sup>2+</sup>-dependent protein kinase C participates in contractile responses of vascular smooth muscle. This study characterizes vascular reactivity to protein kinase C activators in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY). Helical strips of mesenteric arteries were mounted in organ chambers for measurement of isometric contractions (responses were normalized as a percentage of maximal force in response to 100 mM KCl; in SHRSP, 350 ± 16 mg; in WKY, 335 ± 21 ing). Arteries from SHRSP contracted faster and developed greater force than arteries from WKY (168 ± 9% vs 143 ± 3%) in response to the phorbol ester, 12-Otetradecanoylphorbol-13-acetate. Arteries from SHRSP (0.6 × 10-8 M) were more sensitive to the phorbol ester than those from WKY (2.2 × 1(H M), as indicated by the dose of the phorbol ester required to produce 50% of the maximal response to KCl. Additionally, SHRSP arteries were more sensitive to the contractile effects of mezerein, a non-phorbol ester activator of protein kinase C. Ca<sup>2+</sup>-free solution (1.0 mM EGTA) and verapamil (10-7 M) caused relaxation (approximately -60%) of contractions in response to the phorbol ester (10<sup>-1</sup> M). Addition of 10-6 M of the phorbol ester to arteries that were preincubated in Ca<sup>2+</sup>-free solution (1.0 mM EGTA for 30 minutes) elicited submaximal contractions (in SHRSP, 26 ± 4%; in WKY, 38 ± 7%). Upon addition of 1.6 mM Ca<sup>2+</sup>, arteries from SHRSP contracted faster (t<inf>v2</inf>, = 2.7 ± 0.6 minutes) than those from WKY (8.2 ± 0.5 minutes). These data indicate that increased vascular responsiveness in SHRSP may result from enhanced activity of the protein kinase C branch of the Ca<sup>2+</sup> messenger system.

Original languageEnglish (US)
Pages (from-to)III-150-III-154
JournalHypertension
Volume9
Issue number6, Part 2
Publication statusPublished - Jun 1987

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Keywords

  • Mesenteric artery
  • Phorbol ester
  • Protein kinase C
  • Stroke-prone spontaneously hypertensive rats

ASJC Scopus subject areas

  • Internal Medicine

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