piperidines and estradiol-3-benzoate

Anandamide (0.01 to 10 microM) caused greater concentration-dependent reductions of the contractile-induced responses to noradrenaline in female than in male mesenteric vascular beds isolated from adult Sprague-Dawley rats. Greater relaxant responses in females were also induced by the vanilloid TRPV1 receptor agonist capsaicin (0.01 to 10 microM), whereas no sex differences were observed for the relaxations caused by either acetylcholine or sodium nitroprusside. The effect of anandamide in either sex was reduced by the vanilloid TRPV1 receptor antagonist capsazepine but not by the cannabinoid CB1 receptor antagonist N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR141716A). In males, the anandamide-induced relaxations were potentiated by in vitro exposure during 5 min to 0.5 microM 17beta-oestradiol and unmodified by the protein synthesis inhibitor cycloheximide. The vasorelaxant effects of anandamide in female rats were decreased by ovariectomy. This decrease was prevented by in vivo treatment with 17beta-oestradiol-3-benzoate (450 microg/kg i.m., once a week during 3 weeks) and counteracted by in vitro exposure to oestrogen. In vivo treatment with 17beta-oestradiol also potentiated anandamide-induced responses in males. In conclusion, this study shows an oestrogen-dependent sensitivity to the vanilloid TRPV1 receptor-mediated vasorelaxant effects of anandamide in the mesenteric vasculature of Sprague-Dawley rats, that could be mediated by both genomic and non-genomic mechanisms.

Topics: Acetylcholine; Animals; Arachidonic Acids; Argentina; Capsaicin; Chile; Cycloheximide; Dose-Response Relationship, Drug; Drug Synergism; Endocannabinoids; Estradiol; Estrogens; Female; Male; Mesentery; Muscle, Smooth, Vascular; Nitroprusside; Norepinephrine; Ovariectomy; Phenylmethylsulfonyl Fluoride; Piperidines; Polyunsaturated Alkamides; Pyrazoles; Rats; Rats, Sprague-Dawley; Rimonabant; Sex Characteristics; Time Factors; Vasodilation

Adult, hormone-primed, ovariectomized rats (CDF-344) with bilateral implants within the ventromedial nucleus of the hypothalamus (VMN), were injected with 0.5 microgram estradiol benzoate followed 48 h later with 500 microgram progesterone. This priming produced rats with 2 different levels of sexual receptivity. Rats with a lordosis to mount ratio (L/M)>/=0.5 were used to examine the potential lordosis-inhibiting effects of the 5-HT2A receptor antagonist, R(+)-a-(2, 3-dimethoxyphenyl)-1-[2(4-fluoro-phenylethyl)]-4-piperidine-methanol (MDL 100,907), and the 5-HT2C receptor antagonist, 5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2, 3-f]indole (SB 206553). Rats with low sexual receptivity (L/M<0.5) were bilaterally infused with the 5-HT2A/2C receptor agonist, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI), or DOI plus either MDL 100,907 or SB 206553 to determine if either drug would attenuate the lordosis-facilitating effects of DOI. The 5-HT2C receptor antagonist, but not the 5-HT2A receptor antagonist, effectively inhibited lordosis behavior. Similarly, SB 206553 was more effective than MDL 100,907 in reducing the DOI-induced increase in lordosis responding. However, both drugs limited the duration of lordosis responding initiated by DOI. These results are consistent with prior suggestions that 5-HT2A/2C receptors within the VMN are involved in the modulation of lordosis behavior and lead to the suggestion that 5-HT2C, rather than 5-HT2A, receptors are primarily responsible for the effects of 5-HT2 receptor-active drugs on lordosis behavior.

Topics: Animals; Estradiol; Female; Fluorobenzenes; Indoles; Indophenol; Ketanserin; Ovariectomy; Piperidines; Posture; Pyridines; Rats; Rats, Inbred Strains; Receptor, Serotonin, 5-HT2C; Receptors, Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Sexual Behavior, Animal; Ventromedial Hypothalamic Nucleus