Diazoxide, a non-diuretic benzothiadiazlne antihypertensive agent, is thought to act directly upon the vascular smooth muscle of the resistance vessels to exert its therapeutic effects in hypertension. Diazoxide may exert its antihypertensive action by antagonizing calcium in vascular smooth muscle. Wohl et al. (1967 and 1968) have suggested such an interaction based on experiments conducted with isolated rabbit aortae. The present experiments were designed to investigate the possible cellular locus of the postulated interaction of diazoxide with calcium using the isolated anterior mesenteric vein of the rabbit as a model of vascular smooth muscle. This vein is spontaneously motile and possesses characteristics similar to those observed for vessels of the microcirculation. Diazoxide at 10ˉ⁴ M inhibited spontaneous motility and its associated membrane electrical activity, and caused hyperpolarization in rabbit anterior mesenteric veins examined with a sucrose gap apparatus. Diazoxide also inhibited spontaneous electrical and contractile activity in guinea-pig taenia coli and in estrogen dominated rabbit uterus. In all these tissues, calcium is believed to play an important role in spontaneous electrical membrane activity. Diazoxide failed to affect contractility, rate of spontaneous contractions, or action potential configurations in isolated rabbit heart, even though the action potential in heart tissues possesses a definite calcium current component. Diazoxide reduced contractions induced in the mesenteric vein by electrical stimulation of the smooth muscle itself or by excitation of the nerve endings within the vein. Various drugs were chosen for their ability to contract the mesenteric vein in different ways. Noradrenaline contracts vascular smooth muscle even when the tissue Is depolarized with ouabain Diazoxide failed to inhibit noradrenaline contractions in the depolarized vein, but showed the characteristics of a competitive inhibitor of noradrenaline in normally polarized veins. Diazoxide was also capable of inhibiting contractions to serotonin and procaine, agents which require membrane polarization to initiate contraction. The inhibitory effect of diazoxide was not observed to be modified in solutions containing high concentrations of calcium. Diazoxide was tested upon the contractile responses to calcium In veins depolarized in K⁺ Ringer solution. Examination of the resultant dose response curves showed that diazoxide inhibited calcium contractions ln a reversible, non surmountable manner. Hydrochlorothiazide had no effect upon calcium induced contractions. Diazoxide antagonizes drug induced contractions only if a polarized membrane is present. Calcium Induced contractions in depolarizing solutions were inhibited in an apparently Insurmountable manner, while drug responses in polarizing solutions were inhibited by diazoxide in a surmountable manner. In addition, action potentials from rabbit heart were unchanged whereas, the apparently calcium spike mediated electrical activity of certain smooth muscles is inhibited. It is concluded that diazoxide affects the membrane of vascular smooth muscle to reduce excitability of the tissue to drugs or electrical stimuli. It is possible that cell membrane bound calcium could be the locus of action of diazoxide and that this agent modifies membrane calcium to cause increased membrane stability. / Medicine, Faculty of / Anesthesiology, Pharmacology and Therapeutics, Department of / Graduate

No setor de Ginecologia do Hospital das Clínicas da FMUSP, 67 mulheres com leiomiomas do útero e idade de 24 a 39 anos, nuligestas foram estudadas. 31 receberam goserelin a cada 28 dias por 6 meses (grupo I) e 36 não (grupo II). Do grupo I, 16 apresentaram redução volumétrica menor ou igual a 36% (subgrupo Ia) e 15, maior ou igual a 36% (subgrupo Ib). Após a miomectoma, os nódulos foram encaminhados para anatomopatológico. Um único leiomioma de cada mulher foi submetido ao estudo eimuno-histoquímico para avaliação das concentrações de receptores de estrógeno, progesterona, vasos sanguíneos, colágeno, AgNOR e da celularidade. Concluiu-se que o análogo do GnRH está relacionado à diminuição da concentração de receptores de estrógeno. Não apresentou influência uniforme para progesterona, vasos sanguíneos, colágeno e celularidade / From 1994 to 1998, a total of 67 women with leiomyomas in the uterus, aging from 24 to 39, nuliparous and avid for pregnancy were studied in the Department of Gynaecology and Obstetrics of Hospital das Clínicas of Medical School of the University of São Paulo. From these, 31 received Goserelin 3,6mg at each 28 days for six months (group I) and 36 did not received medication (group II or control group). From the pacients who received medication, 16 presented volumetric reduction equal to or less than 36% (subgroup Ia) and the other 15 reduction larger than 36% (subgroup Ib). All women were submitted to myomectomy and the nodes were sent to anatomicopathological study. Only one leiomyoma of each woman was submitted to histochemical and immunohistochemical study to measure the concentrations of receptors of estrogen and progesterone, blood vessels, collagen, AgNOR and cellularity. It was observed that the group that presented larger volumetric reduction after using this medication showed variations of the concentration of receptors of estrogen (p0,001), progesterone (p=0.019), blood vessels (p=0.060), collagen (p=0.048), AgNOR (p=0.321) and number of cells (p=0.221), in comparison to the subgroup Ia and the group II (control group). As a result , it was observed that the GnRH analogue is related to the decrease of the concentration of receptors of estrogen, however it did not present uniform influence in the receptors of progesterone, blood vessels, collagen, and cellularity of this tumor

No setor de Ginecologia do Hospital das Clínicas da FMUSP, 67 mulheres com leiomiomas do útero e idade de 24 a 39 anos, nuligestas foram estudadas. 31 receberam goserelin a cada 28 dias por 6 meses (grupo I) e 36 não (grupo II). Do grupo I, 16 apresentaram redução volumétrica menor ou igual a 36% (subgrupo Ia) e 15, maior ou igual a 36% (subgrupo Ib). Após a miomectoma, os nódulos foram encaminhados para anatomopatológico. Um único leiomioma de cada mulher foi submetido ao estudo eimuno-histoquímico para avaliação das concentrações de receptores de estrógeno, progesterona, vasos sanguíneos, colágeno, AgNOR e da celularidade. Concluiu-se que o análogo do GnRH está relacionado à diminuição da concentração de receptores de estrógeno. Não apresentou influência uniforme para progesterona, vasos sanguíneos, colágeno e celularidade / From 1994 to 1998, a total of 67 women with leiomyomas in the uterus, aging from 24 to 39, nuliparous and avid for pregnancy were studied in the Department of Gynaecology and Obstetrics of Hospital das Clínicas of Medical School of the University of São Paulo. From these, 31 received Goserelin 3,6mg at each 28 days for six months (group I) and 36 did not received medication (group II or control group). From the pacients who received medication, 16 presented volumetric reduction equal to or less than 36% (subgroup Ia) and the other 15 reduction larger than 36% (subgroup Ib). All women were submitted to myomectomy and the nodes were sent to anatomicopathological study. Only one leiomyoma of each woman was submitted to histochemical and immunohistochemical study to measure the concentrations of receptors of estrogen and progesterone, blood vessels, collagen, AgNOR and cellularity. It was observed that the group that presented larger volumetric reduction after using this medication showed variations of the concentration of receptors of estrogen (p0,001), progesterone (p=0.019), blood vessels (p=0.060), collagen (p=0.048), AgNOR (p=0.321) and number of cells (p=0.221), in comparison to the subgroup Ia and the group II (control group). As a result , it was observed that the GnRH analogue is related to the decrease of the concentration of receptors of estrogen, however it did not present uniform influence in the receptors of progesterone, blood vessels, collagen, and cellularity of this tumor