Comparative effects of tramadol on vascular reactivity in normotensive and spontaneously hypertensive rats.
The aim of the present study was to determine the effects of tramadol on vascular reactivity in aortic rings from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Aortic rings, with or without endothelium, were obtained from male WKY rats and SHR (15-20 weeks old) and prepared for isometric tension recording. Aortic rings were precontracted with phenylephrine (10 micromol/L) or 40 mmol/L KCl and then exposed to cumulative concentrations of tramadol (0.1-1 mmol/L). Tramadol produced a concentration-dependent relaxation of precontracted aortic rings from WKY rats and SHR, which was not dependent on functional endothelium. Vascular relaxation was significantly greater in rings from SHR than WKY rats. The concentration of tramadol necessary to produce a 50% reduction of the maximal contraction to phenylephrine (IC(50)) in rings with and without endothelium from SHR was 0.47 +/- 0.08 and 0.44 +/- 0.03 mmol/L, respectively (P = 0.76). Tramadol attenuated the contracture elicited by Ca2+ in depolarized tissue, suggesting that it may inhibit L-type Ca2+ channels. However, pretreatment with nicardipine (1 micromol/L) prevented the relaxation induced by tramadol in aortic rings from WKY rats and partially reduced its inhibitory effect in aortic rings from SHR. 6. Pretreatment of endothelium-denuded aorta with glybenclamide (3 micromol/L), 4-aminopyridine (3 mmol/L), tetraethylammonium (3 mmol/L) and naloxone (100 micromol/L) did not affect tramadol-induced vasodilation of aortic rings from either WKY rats or SHR. Intravenous administration of tramadol (10 mg/kg) to conscious SHR significantly reduced both systolic and diastolic blood pressure from 171.4 +/- 5.3 to 129.3 +/- 5.3 (P = 0.002) and from 125.0 +/- 6.5 to 57.8 +/- 8.9 mmHg (P = 0.003), respectively.
Department of Basic and Clinical Pharmacology, Institute of Biomedical Science, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Juliana M
JM
Raimundo
Luana B
LB
Pontes
Fernanda
F
Antunes
Roberto T
RT
Sudo
Margarete M
MM
Trachez
Gisele
G
Zapata-Sudo
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014147:Tramadol / Q000494:pharmacology* / Q000627:therapeutic use; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology / Q000627:therapeutic use
D014665:Vasodilator Agents; D014147:Tramadol