RESUMEN
Abstract Cyclic nucleotides are important secondary messengers involved in modulating the contractility of various smooth muscles. Phosphodiesterases (PDE) play important roles in this process by modulating the levels of cyclic nucleotides and their duration of action. This study was designed to identify and characterize the PDE isoenzymes in rat urinary bladder and to evaluate their roles in regulating bladder smooth muscle tone. The involvement of cAMP and cGMP pathways in this process was also assessed. The studies were carried out with tissues from male and female rats and no significant sex-related difference was found in the results. Utilizing the unique pharmacological properties of different isoenzymes, PDE1, 2, 3, 4, and 5 were identified in rat bladder. Organ bath experiments showed that forskolin was most potent in relaxing pre-contracted rat bladder strips while sodium nitroprusside was moderately effective, suggesting the relaxation was mainly mediated by the cAMP pathway and that the cGMP pathway is moderately involved. For PDE inhibitors, the non-specific inhibitor papaverine was most effective in relaxing pre-contracted bladder strips. Among isoenzyme-selective inhibitors, vinpocetine, EHNA, and sildenafil induced more relaxation than milrinone and rolipram.
Asunto(s)
Isoenzimas/metabolismo , Hidrolasas Diéster Fosfóricas/metabolismo , Vejiga Urinaria/enzimología , Animales , Colforsina/farmacología , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Femenino , Guanilato Ciclasa/metabolismo , Técnicas In Vitro , Masculino , Contracción Muscular/efectos de los fármacos , Contracción Muscular/fisiología , Donantes de Óxido Nítrico/farmacología , Nitroprusiato/farmacología , Inhibidores de Fosfodiesterasa/farmacología , Ratas , Ratas WistarRESUMEN
The Nurse-Midwifery Division, with the full support of the Department of Obstetrics and Gynecology, and with committed partners in the College of Nursing, is proceeding forward with a three-part mission: nurse-midwifery practice, teaching, and research. Our practice sites are likely to remain varied but stable, with half of our clients being either Hispanic or Native American. Our commitment to nurse-midwifery education is solid, and our participation in the process will continue to take several forms, including the central one of clinical preceptorships. Our research agenda will grow. We hope our experience with GRAVI-DATA will contribute to the development of a national nurse-midwifery data base. Other future goals of our research program include collaboration in multisite clinical research projects, obtaining substantial external funding and recruiting doctorally prepared investigators.
Asunto(s)
Relaciones Interinstitucionales , Modelos de Enfermería , Modelos Organizacionales , Enfermeras Obstetrices/educación , Facultades de Medicina/organización & administración , Bases de Datos Factuales , Educación de Postgrado en Enfermería/organización & administración , New Mexico , Enfermeras Obstetrices/organización & administración , Investigación en EnfermeríaRESUMEN
The optical isomers and deoxy form of 2-(3,4, alpha-trihydroxybenzyl)imidazoline hydrochloride were examined for their alpha-adrenergic activity on rat aorta. The rank order of stimulant activity was deoxy (2) congruent to (R)-(-)-1 greater than (S)-(+)-1. This is in contrast to catecholamines in which the order of activity is (R)-(-)-epinephrine greater than (S)-(+)-epinephrine = epinine (deoxyepinephrine). The relative order of potency for the isomers of 2-(3,4, alpha-trihydroxybenzyl)imidazoline is different than that predicted by the Easson--Stedman theory for stereoisomers of catecholamines. Also, substitution of the deoxy compound 2 with substituents, methyl or benzyl, in the 4-position lowers the alpha-adrenergic agonist activity, and differences observed between optical isomers were small.
