A study of the mechanisms involved in relaxation induced by 17-beta-estradiol in the isolated rabbit aorta.

We used the isolated rabbit aorta to examine the mechanisms that mediate the known vasodilatation induced by 17-beta-estradiol. Our results suggest that nitric oxide (NO), the inhibition of Ca2+ release from intracellular stores through the IP3 pathway and Ca2+ influx through potential-dependent calcium channels (PDCs) seem to be involved. Prostaglandins and adrenergic beta receptors do not influx, intracellular Ca2+ release, NO, cyclic guanine monophosphate (cGMP), prostaglandins and adrenergic beta receptors.

Effect of progesterone on the contractile response of isolated pulmonary artery in rabbits.

The purpose of this study was to assess the direct effect of progesterone on rabbit pulmonary arteries and to examine the mechanism of its action. Rings of pulmonary artery from male rabbits were suspended in organ baths containing Krebs solution, and isometric tension was measured. The response to progesterone was investigated in arterial rings contracted with noradrenaline (NA), KCl, and CaCl2. The effects of endothelium, nitric oxide (NO), prostaglandins, cyclic GMP (cGMP), and the adrenergic beta-receptor on progesterone-induced relaxation were also assessed. Progesterone inhibited the vasocontractivity to NA, KCl, and CaCl2, and relaxed rabbit pulmonary artery. The relaxing response of progesterone in pulmonary artery was significantly reduced by removal of endothelium, inhibitors of nitric oxide synthase and guanylate cyclase, but not by prostaglandin synthase inhibitor and blockage of the adrenergic beta-receptor. In Ca2+-free (0.1 mM EGTA) Krebs solution, progesterone inhibited NA-induced contraction that was intracellular Ca2+-dependent, but didn't affect the contraction of extracellular Ca2+-dependent component. Our results suggest that progesterone induces relaxation of isolated rabbit pulmonary arteries partially via NO and cGMP. Progesterone may also inhibit Ca2+ influx through potential-dependent calcium channels (PDCs) and Ca2+ release from intracellular stores.

Agouti-related protein is a mediator of diabetic hyperphagia.

To explore the role of agouti-related protein (AGRP) in diabetic hyperphagia changes in hypothalamic AGRP mRNA levels were examined in diabetic rats. Rats rendered diabetic by streptozotocin displayed marked hyperglycemia (blood glucose 456.0+/-8.4 mg/dl versus 71.8+/-1.9 mg/dl) and hyperphagia (36.9+/-1.0 g/day versus 22.0+/-0.4 g/day), that was associated with a 286.6+/-4.4% increase in hypothalamic AGRP mRNA and a 178.9+/-13.5% increase in hypothalamic NPY mRNA. Insulin treatment of diabetic rats partially corrected blood glucose (147.4+/-13.1 mg/dl) and ameliorated hyperphagia (26.6+/-2.0 g/day). Insulin replacement was also associated with a return of hypothalamic AGRP mRNA (111.7+/-8.3% of controls) and NPY mRNA (125.0+/-8.9% of controls) from the elevated levels that were observed in untreated diabetic rats. In contrast to insulin treated rats, sodium orthovanadate treated diabetic rats remained significantly hyperglycemic (361.5+/-12.5 mg/dl). However, despite their persistent hyperglycemia, orthovanadate treated diabetic rats were still observed to have a significant reduction of hypothalamic AGRP mRNA (138.7+/-11.4%) and NPY mRNA (129.9+/-9.8%). Simultaneous measurement of serum leptin revealed suppressed levels in both untreated diabetic (0.5+/-0.1 ng/ml) and sodium orthovanadate treated rats (0.5+/-0.1 ng/ml) compared to non-diabetic controls (2.1+/-0.1 ng/ml). These data indicate that AGRP is a mediator of diabetic hyperhpagia and suggest that insulin can directly influence hypothalamic AGRP and NPY mRNA expression.

Agouti-related protein-like immunoreactivity: characterization of release from hypothalamic tissue and presence in serum.

A novel RIA was used to examine the release of agouti-related protein-like immunoreactivity (AGRP-LI) from perfused rat hypothalamic tissue slices and to characterize AGRP-LI in rat serum. A continuous low level basal AGRP-LI release was observed from hypothalami of rats fed ad libitum before the rats were killed. Basal AGRP-LI release was 3-fold greater in rats fasted 48 h. In fasted animals leptin dose-dependently suppressed basal AGRP-LI release. In fed animals no change in basal AGRP-LI release was detected in response to 10(-6) M alpha-MSH, orexin B, melanin-concentrating hormone, or serotonin. HPLC analysis of AGRP-LI in rat serum identified a single peak that eluted in close proximity to synthetic AGRP (87-132) and mouse [Leu127Pro]AGRP and that was identical to the peak seen in hypothalamic and adrenal tissue extracts. The serum concentration of AGRP-LI in rats fed ad libitum was 0.865+/-0.323 nmol/liter (mean +/- SE). Food deprivation resulted in a slow, but statistically significant rise in serum immunoreactivity at 48 h [1.174+/-0.118 nmol/liter (mean +/- SE)]. Bilateral adrenalectomy did not change serum levels of AGRP-LI. These studies demonstrate that in the rat there are different levels of basal hypothalamic AGRP-LI release in fed and fasted states and that in the fasted rat this release can be profoundly suppressed by leptin. These studies also suggest that AGRP is present in the systemic circulation of rats.

[Effect of motherwort herb on the myoelectric activity of uterus in rats].

OBJECTIVE: To investigate the effect of motherwort herb on the myoelectric activity of uterus in rats. METHOD: A pair of bipolar Ag-AgCl electrode was implanted on the serosal surface of the uterus in rats, motherwort herb was injected intra-abdominal cavity in rats in dose of 0.1 ml, 0.2 ml and 0.4 ml respectively, and the changes of uterine myoelectric activity were observed. RESULT: Motherwort herb significantly increased the frequency and average amplitude of uterus slow waves of in rats. The frequency and maximum amplitude of single waves also obviously increased. The time course of outbreak waves was prolonged, the series intervals were reduced and the maximum amplitude in each outbreak was increased. CONCLUSION: The exciting effect of motherwort herb on the uterine smooth muscle may have something to do with the alteration of the ion concentration in relation to myoelectric activity, resulting in the increase of myoelectric activity of pacesetter cells as well as in the acceleration of depolarization of spike activity.

[Effect of cholecystokinin and secretin on contractile activity of isolated gastric muscle strips in guinea pigs].

Motility of gastric strips taken from different regions of guinea pig stomach were simultaneously recorded in 8 tissue chambers to test the effect of cholecystokinin-octapeptide (CCK-8) and secretin. It was found that CCK-8 could increase (1) all regional circular and longitudinal muscular tension at rest, (2) the frequency of contractions in body, antrum and pylorus, (3) the mean contractile amplitude of antral circular strips, (4) the motility index of pylorus, but decrease the mean contractile amplitude of body and antral longitudinal strips. All the CCK-8 effects could not be blocked by atropine or indomethacin. Secretin was without effect on gastric smooth muscle activity.

[The physiologic disposition and pharmacokinetics of guaiacol acetylsalicylate in rats].

Guaiacol acetylsalicylate (GASL) has been shown to possess significant anti-inflammatory, antipyretic and expectorant activities and has been used clinically in chronic bronchitis with fairly good results. In the present work, the absorption, distribution and excretion of metabolites of the drug were studied in rats using quantitative TLC scanning technique. GASL was shown to be unstable in rat gastrointestinal tract and guaiacol salicylate (GSLT) and salicylic acid (SLA) were found in plasma. The plasma SLA concentration-time curve obtained after oral administration of GASL to rats was shown to fit a one compartment open model with the following pharmacokinetic parameters: T1/2ka = 1.25 h, T1/2ke = 3.28 h, ka = 0.5554/h, ke = 0.2111/h, Tmax = 3.02 h, Cmax = 331.46 micrograms/ml, AUC = 2832.93 micrograms/ml.h The SLA concentration was found to be high in muscle, moderate in spleen, testicle, kidney, lung, plasma, heart and liver and low in brain. The GSLT concentration was found to be low in plasma and organs. Within 24 h following ig administration of GASL the total SLA excreted in urine and feces was 10.9 and 0.41 of the GASL dose, respectively.