CoenzymeA glutathione disulfide is a potent modulator of angiotensin II-induced vasoconstriction.
CoenzymeA glutathione disulfide (CoASSG) has recently been isolated from bovine adrenal glands and is assumed to play an important role in blood pressure (BP) control. We used the isolated perfused rat kidney to investigate the modulating effects of CoASSG on angiotensin II (AngII)-induced vasoconstriction. Permanent perfusion with CoASSG (1 micromol/L) for 60 min induced a significant (P < .05) shift to the left in the dose-response curve for AngII (about 3.1-fold), whereas the dose-response curve for norepinephrine (NE) was unaffected. During continuous perfusion with 1 micromol/L CoASSG, the repetitive application of 10 pmol AngII significantly increased its vasoconstriction by 170% +/- 14% (P < .05) and 235% +/- 50% (P < .05) for 60 and 120 min, respectively. The potentiation of AngII by permanent perfusion with CoASSG is dose- and time-dependent and shows a plateau at 120 min. Glutathione, oxidized coenzymeA, and coenzymeA (each 1 micromol/L) are not able to enhance the vasoconstriction induced by AngII. We conclude that CoASSG is able to potentiate the vasoactive properties of AngII, and that CoASSG might play an important role in BP regulation via modulating effects of AngII.
Ruhr-Universität Bochum, Universitätsklinikum, Medizinische Klinik I, Herne, Germany.
M
M
van der Giet
A
A
Schmid
J
J
Jankowski
H
H
Schlüter
W
W
Zidek
M
M
Tepel
D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D003065:Coenzyme A / Q000494:pharmacology / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D010477:Perfusion; D051381:Rats; D011921:Rats, Inbred WKY; D013777:Tetrazoles / Q000494:pharmacology; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014666:Vasomotor System / Q000187:drug effects
D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; C019305:coenzyme A-glutathione mixed disulfide; C066026:losartan carboxylic acid; D019808:Losartan; D003065:Coenzyme A