Activation of protein kinase C and nicotinamide adenine dinucleotide phosphate oxidase in leukocytes of spontaneously hypertensive rats.
The involvement of oxidative stress in polymorphonuclear leukocytes (PMN) in the pathogenesis of hypertension remains to be elucidated. We analyzed the generation of reactive oxygen species (ROS) by the circulating and peritoneally infiltrating PMN from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). Flow cytometric analysis revealed that ROS generation by PMN from SHR was higher than that from WKY before (at 6 weeks of age) and after (at 16 weeks of age) the onset of hypertension. In vivo, ROS generation by PMN from SHR, but not that by PMN from WKY, was significantly suppressed by 10-week treatment with 50 mg/kg/day carvedilol, and this treatment did not affect blood pressure. Western blotting analysis revealed that protein kinase C alpha (PKCalpha), but not PKCbetaI or betaII, was activated more strongly in PMN from SHR than in PMN from WKY. Furthermore, expression of p47phox of nicotinamide adenine dinucleotide phosphate oxidase, but not of p67phox, in PMN from SHR was higher than that in PMN from WKY. These results suggest that ROS generation by PMN is principally enhanced in SHR through activation of PKCalpha and p47phox.
Maeda
Kensaku
K
Department of Biochemistry and Molecular Pathology, Osaka City University Medical School, Osaka, Japan. maedahk@med.osaka-cu.ac.jp
Yasunari
Kenichi
K
Sato
Eisuke F
EF
Yoshikawa
Junichi
J
Inoue
Masayasu
M
D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D015153:Blotting, Western; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009504:Neutrophils / Q000201:enzymology*; D010750:Phosphoproteins / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000378:metabolism
D018674:Adrenergic Antagonists; D000959:Antihypertensive Agents; D000975:Antioxidants; D002227:Carbazoles; D004791:Enzyme Inhibitors; D010750:Phosphoproteins; D011412:Propanolamines; D017382:Reactive Oxygen Species; D000077261:Carvedilol; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha