Vascular responsiveness to phorbol esters in coarctation-hypertensive rats.
Recent observations suggest that a phospholipid-sensitive, calcium-dependent protein kinase affects the contractile responses of vascular smooth muscle. Protein kinase C activators such as the tumor-promoting phorbol esters have been used as tools to study protein kinase C function in various intact cells. The present study characterizes vascular reactivity to protein kinase C activation in rats made hypertensive by coarctation of the abdominal aorta. Thoracic aortic strips from hypertensive rats developed greater force than arteries from normotensive rats in response to the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). Thoracic aortae from hypertensive rats were more responsive (lower threshold dose) to the phorbol ester than those from normotensive rats. Additionally, arteries from hypertensive rats were more responsive to the contractile effects of mezerein, a non-phorbol ester activator of protein kinase C. Removal of the endothelium did not eliminate the difference in responsiveness to TPA in thoracic aortae from normotensive and hypertensive rats. The threshold dose of TPA in abdominal aortae from hypertensive rats was not different from that in normotensive rats. However, the maximal response to 10(-6) mol/l TPA after 60 min in abdominal aortae from hypertensive rats was significantly less than that in aortae from normotensive rats. Thus, contractile responses to TPA appear to be influenced by arterial pressure per se. The inhibitory effects of the calcium antagonist, verapamil, in thoracic aortae from hypertensive rats were greater than in those from normotensive rats. Verapamil inhibited TPA-induced contractions in abdominal aortae from hypertensive rats to the same extent as in those from normotensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Turla
M B
MB
Department of Physiology, University of Michigan Medical School, Ann Arbor 48109-0622.
Park
S M
SM
Webb
R C
RC
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001017:Aortic Coarctation / Q000150:complications; D002273:Carcinogens / Q000494:pharmacology; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000209:etiology / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013729:Terpenes / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002273:Carcinogens; D004224:Diterpenes; D010703:Phorbol Esters; D013729:Terpenes; C011309:mezerein; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate