1. Contractile responses of smooth muscle from the Wistar rat urinary bladder were studied with the use of muscarinic agonists and antagonists. 2. McN-A-343 induced only weak contractile responses of the bladder muscle. In contrast, oxotremorine showed higher potency than either acetylcholine or bethanechol in inducing a contractile response (the respective pD2 values were 6.38 +/- 0.25, 4.82 +/- 0.24 and 4.42 +/- 0.14). 3. The M2 antagonists, methoctramine (10(-9) M to 10(-5) M) and gallamine (10(-9) M to 10(-5) M), did not reduce acetylcholine-induced (10(-5) M) contractions of the bladder muscle strip. On the other hand, 4-diphenyl-acetoxy-N-methyl piperidine methiodide (4-DAMP, 10(-10) M to 10(-7) M), an M3 receptor blocker, effectively antagonized the acetylcholine-induced contractions in a concentration-dependent manner. 4-DAMP had a similar pA2 value to those of the non-selective antagonists, atropine and scopolamine (pA2 values were 8.26 +/- 0.05, 8.36 +/- 0.05 and 8.41 +/- 0.11, respectively). Pirenzepine, and M1 blocker, antagonized the contractions at higher concentrations (10(-8) M to 10(-5) M, pA2 = 6.23 +/- 0.04). 4. It is concluded that (1) the dominant muscarinic receptor subtype responsible for smooth muscle contraction in the rat urinary bladder is M3; and (2) the muscarinic agonist oxotremorine was more potent than acetylcholine and bethanechol in inducing a contractile response.
Clinically, a 59% prevalence of impotence was reported among diabetic male patients. Neurological, vascular, endocrinologic and psychological factors are probably involved. Previous reports with the rat model found deterioration of sexual behavior and reproductive function caused by streptozotocin (STZ)- induced diabetes. The purpose of the present study was to develop the dark-cycle video recording methodology for the observation of rat sexual activities and to study the effect of STZ-induced diabetes on sexual performances of the rat. Adult male Wistar rats were rendered diabetic with intraperitoneal injection of STZ (60 mg/kg body weight). In the 4th week a diabetic rat or a control rat was caged with an adult ovariectomized female rat during the dark cycle. The female had been brought into behavioral estrus with intramuscular injection of 0.1 mg estradiol benzoate 3 days before and 1.0 mg progesterone 3 h before testing. Infrared-light-illuminated video recording was performed to evaluate the sexual performances. The mounting latency and frequency, intromission latency and frequency, the hit rate as well as the post-ejaculatory period of the diabetic rats were significantly deteriorated when compared with the controls (p < 0.05). However, the ejaculatory latency showed no significant difference between the two groups (p > 0.05). In conclusion, it has been demonstrated that with this methodology, behavioral studies on nocturnal animals like the rat can be carried out conveniently. It was shown that the sexual arousal mechanism and copulation-ejaculatory mechanism were both depressed in STZ-induced diabetic rats. The same study model can be used for further pathophysiological and pharmacological researches on the sexual behaviors of diabetic rats.
The treatment effect of ‘ryu-wei-ti-huang-wan’, a Chinese prescription composed of extracts from six plants, on diabetic impotence was evaluated in the present study. Adult male Wistar rats were divided into three groups: (1) rats rendered diabetic with a single intraperitoneal injection of streptozotocin (60 mg/kg body weight); (2) rats with streptozotocin-induced diabetes treated with a ryu-wei-ti-huang-wan powder preparation at a dose of 30 mg powder/kg body weight twice a day, and (3) control rats. A male rat was caged with an adult ovariectomized female rat during the dark cycle. Infra-red-light-illuminated video recording was utilized to evaluate the sexual performance. The diabetic rats exhibited depressed mounting activity and no intromission or ejaculation. After ryu-wei-ti-huang-wan treatment either for 1 day or 2 weeks, the diabetic rats showed significant improvement in mounting performance with preservation of intromission and ejaculation. No significant difference in the blood sugar level was noted between the treatment and non-treatment groups. In conclusion, the diabetic rats showed impairment in sexual arousal, erectile as well as ejaculatory functions. Ryu-wei-ti-huang-wan was effective in preserving these functions with a rapid onset. It is evident that the extracts exert the therapeutic effects not through a lowering of blood sugar. These substances are potentially useful in the clinical treatment of male diabetic impotence.
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