Mitochondrial coupling factor 6 as a potent endogenous vasoconstrictor.
We demonstrated recently that coupling factor 6, an essential component of the energy-transducing stalk of mitochondrial ATP synthase, suppresses the synthesis of prostacyclin in vascular endothelial cells. Here, we tested the hypothesis that coupling factor 6 is present on the cell surface and is involved in the regulation of systemic circulation. This peptide is present on the surface of CRL-2222 vascular endothelial cells and is released by these cells into the medium. In vivo, the peptide circulates in the vascular system of the rat, and its gene expression and plasma concentration are higher in spontaneously hypertensive rats (SHRs) than in normotensive controls. Elevation of blood pressure with norepinephrine did not affect the plasma concentration of coupling factor 6. Intravenous injection of recombinant peptide increased blood pressure, apparently by suppressing prostacyclin synthesis, whereas a specific Ab to coupling factor 6 decreased systemic blood pressure concomitantly with an increase in plasma prostacyclin. Interestingly, the antibody's hypotensive effect could be abolished by treating with the cyclooxygenase inhibitor indomethacin. These findings indicate that mitochondrial coupling factor 6 functions as a potent endogenous vasoconstrictor in the fashion of a circulating hormone and may suggest a new mechanism for hypertension.
Osanai
T
T
The Second Department of Internal Medicine, Hirosaki University School of Medicine, Hirosaki, Japan. osanait@cc.hirosaki-u.ac.jp
Tanaka
M
M
Kamada
T
T
Nakano
T
T
Takahashi
K
K
Okada
S
S
Sirato
K
K
Magota
K
K
Kodama
S
S
Okumura
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001920:Bradykinin / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology; D011464:Epoprostenol / Q000096:biosynthesis; D015870:Gene Expression; D008297:Male; D008928:Mitochondria / Q000378:metabolism*; D025261:Mitochondrial Proton-Translocating ATPases / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D008969:Molecular Sequence Data; D010086:Oxidative Phosphorylation Coupling Factors / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011993:Recombinant Fusion Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology
D010086:Oxidative Phosphorylation Coupling Factors; D011993:Recombinant Fusion Proteins; D014662:Vasoconstrictor Agents; D011464:Epoprostenol; C000628217:F(6) ATPase; D025261:Mitochondrial Proton-Translocating ATPases; D001920:Bradykinin