Oxybutynin chloride exerts a moderate anticholinergic effect on rabbit detrusor in vitro, which is reversible and competitive in nature (Kg = 4.7 × 10–9), and midway in potency between atropine and papaverine. In addition, oxybutynin strongly antagonizes BaCl2-induced spasms of detrusor with a potency equivalent to that of papaverine and 10 times that of atropine. This musculotropic spasmolytic effect is slightly greater in rabbit than human or monkey tissue, and noncompetitive (pD2 = 5.5). This direct relaxant effect, unlike that of papaverine, is not mediated by the inhibition of tissue phosphodiesterase, but probably reflects oxybutynin’s local anesthetic properties and associated effects on Ca++ fluxes and binding.
The various effects of histamine on smooth muscles and other tissues are thought to be mediated by two pharmacologically distinct receptors, Ht and H2 types. These receptors are defined in terms of their susceptibility to blockade by pyrilamine (typeíi!) or burimamide (typeH2). In this study selective antagonism of the spasmodic effects of histamine on isolated strips of rabbit detrusor has shown that the response is mediated by H1 receptors, with no evidence of H2 activity. The pA2 of the pyrilamine-histamine antagonism is 9.3. The histamine response is susceptible to muscarinic blockade (atropine and propantheline) but not to nicotinic blockade (hexamethonium). Adrenergic blocking agents propranolol (10–4M) and phenoxybenzamine (10–8M) do antagonize the contractile response, but this does not appear to be indicative of adrenergic mediation.
The purpose of this study was to determine the effects of infused vasoactive intestinal polypeptide (VIP) upon reproductive function in the female rabbit. Intravenous infusions of VIP (37.5, 75, and 150 pmol/kg per min) induced acute dose-dependent increases in plasma progesterone (P) but not estradiol (E2) or testosterone (T) in estrous rabbits. This P effect was not associated with an increase in plasma prolactin (Prl) and was not altered by pretreatment with a Prl-inhibiting regimen of bromocriptine. In rabbits stimulated to ovulate with 75 IU human chorionic gonadotropin (hCG) and coitus, plasma P and E2 increased, reaching a peak at 180 min following stimulation. VIP (75 pmol/kg per min) infused from 120 to 180 min following the ovulatory stimuli increased this P peak but did not effect E2 levels. This VIP infusion had no effect upon fertility or upon the number of corpora lutea, uterine implants, or viable conceptuses. Infusions of VIP for 60 min at the P peak, and for 240 min at the time of ovulation, had no significant effect upon ovum pickup or the rate of ovum transport. These observations suggest that 1) VIP infusions in rabbits can increase plasma P from both the basal levels of estrus and from the peak levels preceding ovluation. 2) Infusions of VIP at the time of the preovulatory steroid surge or during ovulation have little effect upon fertility or gamete transport in the rabbit. 3) Endogenous VIP may play a role in the regulation of P secretion in the rabbit.
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