A comparison of pentazocine and morphine for pediatric premedication.
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Biomedical subjects
Publications and source records attributed to R M Levin.
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Erectile function (erection and detumescence) involves the complex interaction of direct neuronal stimulation of corporal smooth muscle, neurohumoral release of specific endothelial contractile and relaxant factors, and secondary modulation by a variety of putative neuropeptides and vasoactive modulators including nitric oxide. The specific aim of the current study was to determine the relative contribution of nitric oxide, adrenergic, purinergic, and cholinergic stimulation in the relaxant response to field stimulation. The results demonstrate that virtually all of the inhibitory effects of field-stimulated relaxation could be explained by the release of nitric oxide. L-NAME (L-NG-nitro arginine methyl ester, a competitive inhibitor of NO synthase) reduced field-stimulated relaxation by over 95% at all frequencies. Neither atropine nor propranolol (or the combination of the two) had any significant effect on field-stimulated relaxation. L-NAME blocked both field-stimulated relaxation and bethanechol-stimulated relaxation. However, methylene blue (a guanyl cyclase inhibitor) was significantly more potent at blocking bethanechol-stimulated relaxation than field-stimulated relaxation. Neither L-NAME nor methylene blue had any effect on nitroprusside (a direct liberator of NO) nor ATP-stimulated relaxation. Isoproterenol had only a minor inhibitory effect on phenylephrine-contracted tissue. These data suggest that 1) Methylene blue, which inhibits guanyl cyclase, is a relatively poor inhibitor of field-stimulated relaxation. 2) L-NAME is a potent inhibitor of NO synthesis and can in a dose-dependent fashion inhibit over 95% of field-stimulated relaxation. 3) Equipotent relaxation of corporal smooth muscle can be effected through pharmacologic stimulation with ATP (2 mM), nitroprusside (200 microM), and field stimulation (32 Hz).(ABSTRACT TRUNCATED AT 250 WORDS)
Erectile function (erection and detumescence) involves the complex interaction of direct neuronal stimulation of corporal smooth muscle, neurohumoral release of specific endothelial contractile and relaxant factors, and secondary modulation by a variety of putative neuropeptides and vasoactive modulators. The net result is a rapid and sustained relaxation of the smooth muscle elements during erection and contraction of the smooth muscle during detumescence. Proper function of the corporal tissue is dependent upon cellular metabolism of glucose and the generation of cellular energy in the form of high energy phosphates. The current study characterizes the following metabolic parameters of the rabbit corpus cavernosum: Tissue concentrations of creatine phosphate (CP), ATP, ADP, and AMP; maximal rate of glucose metabolism to lactic acid and CO2; and activities of the enzymes creatine kinase (CK), citrate synthase, and malate dehydrogenase. For comparative purposes only, bladder smooth muscle preparations were analyzed simultaneously with and under the same conditions as the corpus cavernosum. The results are as follows: The concentrations of ATP and CP in the corpora were significantly lower than the concentrations in bladder. In the corpora, the tissue concentration of CP was lower than the tissue concentration of ATP, whereas the concentration of CP in the bladder was higher than the concentration of ATP. The rate of glucose metabolism to lactic acid and to carbon dioxide was similar for both bladder smooth muscle and corpus cavernosum. The maximal enzymatic activity of the mitochondrial enzyme citrate synthase was similar for both tissues; similarly, there was no significant difference in the activity of malate dehydrogenase between the two tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
Erection is mediated by relaxation of the smooth muscle elements within the sinusoids of the corpus cavernosum. Although cavernosal relaxation can be mediated by a variety of mechanisms including purinergic stimulation, prostoglandins, and beta-adrenergic stimulation the major mechanism involves the stimulated release of nitric oxide (NO) and subsequent relaxation of the corporal smooth muscle. Experimentally, NO can be released both by direct stimulation of NO-containing nerves (using field stimulation) and indirectly via cholinergic stimulation of NO release from the endothelium (using bethanechol). Preliminary studies have indicated that NO release and/or NO-stimulated relaxation of corporal smooth muscle is an active process involving both an increase in cytosolic calcium and an increase in metabolic energy utilization. Ryanodine is a pharmacological agent that can inhibit calcium-stimulated calcium release from the sarcoplasmic reticulum. The results of the current study demonstrated that ryanodine inhibited both field-stimulated relaxation and bethanechol-stimulated relaxation but did not affect relaxation induced by adenosine triphosphate (ATP) or nitroprusside. These studies strongly support the hypothesis that NO-stimulated relaxation is mediated, in part, by calcium release from the sarcoplasmic reticulum through ryanodine-sensitive channels.