Modulation of protein kinase C in aorta of spontaneously hypertensive rats with enalapril treatment.
We measured protein kinase C (PKC) activity, levels of PKC alpha enzyme and PKC alpha mRNA in aortic media of spontaneously hypertensive rats (SHR), normotensive Wistar Kyoto rats (WKY) and enalapril treated SHR (enal-SHR) to examine whether hypotensive treatment of enalapril modulates PKC in aortic media of SHR. The cytosolic PKC activity in crude samples of aortic media of SHR was higher than in those of WKY or enal-SHR (p < 0.01) and was closely associated with blood pressure (r = 0.84, p < 0.001). The membrane PKC activity was detected in samples of SHR, but virtually no activity was detected in samples of WKY or enal-SHR. The cytosolic PKC activity in DEAE column purified samples of SHR was also higher than in those of WKY or enal-SHR (p < 0.01). The PKC alpha enzyme levels (74-kDa and 77-kDa protein) detected by immunoblot were higher in SHR than in WKY or enal-SHR (p < 0.01). The mRNA levels of PKC alpha were higher in SHR than in WKY (p < 0.01) and were much decreased in enal-SHR (p < 0.01). Thus, PKC activity, PKC alpha and its mRNA levels were higher in aortic media of SHR than those in WKY and these increased levels were reversed with enalapril treatment. Considering the pivotal roles of PKC in the mechanism of cellular proliferation and the pathogenesis of hypertension, these results provide clues in understanding the pathogenesis of hypertension, mechanisms of vascular hypertrophy in hypertension and the beneficial effects of angiotensin converting enzyme inhibitor in the treatment of hypertension.
Kanayama
Y
Y
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Negoro
N
N
Okamura
M
M
Konishi
Y
Y
Nishimura
M
M
Umetani
N
N
Inoue
T
T
Takeda
T
T
D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000201:enzymology; D001483:Base Sequence; D004656:Enalapril / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000201:enzymology; D016018:Least-Squares Analysis; D008297:Male; D008969:Molecular Sequence Data; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D012333:RNA, Messenger; D004656:Enalapril; D011493:Protein Kinase C