Enhanced vascular reactivity to protein kinase C activators in genetically hypertensive rats.
Recent studies suggest that phospholipid-sensitive, Ca2+-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 mg). 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-O-tetradecanoylphorbol-13-acetate. Arteries from SHRSP (0.6 X 10(-8) M) were more sensitive to the phorbol ester than those from WKY (2.2 X 10(-8) 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. Ca2+-free solution (1.0 mM EGTA) and verapamil (10(-7) M) caused relaxation (approximately -60%) of contractions in response to the phorbol ester (10(-6) M). Addition of 10(-6) M of the phorbol ester to arteries that were preincubated in Ca2+-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 Ca2+, arteries from SHRSP contracted faster (t1/2 = 2.7 +/- 0.6 minutes) than those from WKY (8.2 +/- 0.5 minutes).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001808:Blood Vessels / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D004224:Diterpenes; D004789:Enzyme Activation; D006973:Hypertension / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011919:Rats, Inbred Strains / Q000502:physiology*; D011921:Rats, Inbred WKY; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014661:Vasoconstriction
D004224:Diterpenes; D013729:Terpenes; C011309:mezerein; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium