Tert-butyl hydroperoxide-mediated vascular responses in DOCA-salt hypertensive rats.
tert-Butyl hydroperoxide (t-BOOH), a membrane permeant oxidant, elicits enhanced vasoconstriction of perfused kidney and mesenteric arterial beds isolated from DOCA-salt-induced hypertensive rats. We hypothesize that enhanced vasoconstriction to t-BOOH during DOCA-salt hypertension involves free radical species and decreases in the expression of the endogenous antioxidant enzyme, superoxide dismutase (SOD). t-BOOH (0.01-50 micromol) dose-dependently constricted the perfused kidney and mesenteric vascular beds (MVB) of rats. Infusion of tempol (100 microM), a free radical scavenger, reduced the constrictor responses from 116.70+/-16.65% to 57.45+/-9.25% (kidneys) and from 72.91+/-3.70% to 48.10+/-0.10% (mesenteric beds). t-BOOH-induced vasoconstriction of both vascular beds were also significantly reduced in DOCA-salt rats treated chronically (15 mg/kg ip, 3 weeks) with tempol (DOCA/TEMPOL). Catalase (500 IU) did not attenuate t-BOOH-induced responses in vascular beds of DOCA/TEMPOL rats. Western blot analyses showed significant reduction in Cu/Zn-SOD expression in DOCA-salt versus sham rats of both vascular preparations; SOD expressions were protected from down-regulation in DOCA/TEMPOL vascular beds. This study suggests that free radical species is involved in both t-BOOH-induced constrictions and in the down-regulation of SOD protein expressions during DOCA-salt hypertension.
Awe
Sunday O
SO
Department of Physiology and Biophysics, Health Sciences Center, University of Louisville, KY 40292, USA.
Tsakadze
Nina L
NL
D'Souza
Stanley E
SE
Adeagbo
Ayotunde S O
AS
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003497:Cyclic N-Oxides / Q000627:therapeutic use; D003900:Desoxycorticosterone; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013113:Spin Labels; D013482:Superoxide Dismutase / Q000096:biosynthesis; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D020122:tert-Butylhydroperoxide / Q000494:pharmacology*
D003497:Cyclic N-Oxides; D005609:Free Radicals; D013113:Spin Labels; D003900:Desoxycorticosterone; D020122:tert-Butylhydroperoxide; D013482:Superoxide Dismutase; C001803:tempol