12-deoxyphorbol-13-isobutyrate-20-acetate and Hypertension

Stimulation of phosphatidylinositol metabolism by neurotransmitters produces diacylglycerol, an activator of protein kinase C, which may be involved in hormone-mediated contractions. We studied the effect of a tumor-promoting phorbol ester, 12-deoxyphorbol 13-isobutyrate 20-acetate (DPBA), on contraction of caudal artery rings of Wistar-Kyoto control (WKY) and spontaneously hypertensive rats (SHR) in order to examine whether protein kinase C-mediated mechanisms are increased in SHR. Although DPBA alone did not produce contractions of either WKY or SHR caudal artery rings, it greatly potentiated the contractions evoked by norepinephrine, norepinephrine, vasopressin, potassium, and calcium ionophore A23187. The potentiation of contractile response to these agents by DPBA was dependent on extracellular calcium. The DPBA potentiation of contractions evoked by norepinephrine, vasopressin, and potassium was significantly greater (p less than 0.05) in SHR than in WKY, while no differences were observed between strains for the contractions evoked by calcium ionophore A23187. These results indicate that the protein kinase C-mediated responses are increased in SHR caudal artery rings, and this effect appears to be due to increased calcium influx through cell membrane calcium channels.

Topics: Animals; Diglycerides; Drug Synergism; Glycerides; Hypertension; Ion Channels; Male; Muscle Contraction; Muscle, Smooth, Vascular; Phorbol Esters; Protein Kinase C; Rats; Rats, Inbred SHR; Rats, Inbred WKY