Investigation of relaxant effects of propofol on sheep sphincter of Oddi.

BACKGROUND/AIMS: Intravenous anesthetics are often used for conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincter of Oddi (SO) manometry. This study was designed to investigate the effects of propofol on sheep SO. METHODS: SO rings were mounted in a tissue bath and tested for changes in isometric tension in response to propofol (10(-8)-10(-4)M) in the presence or absence of L-NAME (3 x 10(-5)M), a non-specific inhibitor of nitric oxide (NO) synthase; indomethacin (10(-5)M), an inhibitor of cyclooxygenase; glibenclamide (10(-5)M), an inhibitor of ATP-sensitive potassium channels; tetraethylammonium (3 x 10(-4)M), inhibitors of calcium-activated potassium channels; 4-aminopyridine (10(-3)M), a voltage-dependent potassium channel blocker. Furthermore, we investigated the Ca(2+) antagonist feature of propofol in precontracted SO rings by CaCl(2). RESULTS: Carbachol (10(-9)-10(-5)M) induced concentration-dependent contraction responses in the SO rings. Propofol (10(-8)-10(-4)M) produced concentration-dependent relaxation on isolated SO rings precontracted by carbachol (10(-6)M). Preincubation of SO rings by L-NAME (3 x 10(-5)M), indomethacin (10(-5)M), glibenclamide (10(-5)M), and 4-aminopyridine (10(-3)M) did not produce a significant alteration on propofol-induced relaxation responses (p > 0.05), while preincubation by tetraethylammonium (3 x 10(-4)M) significantly decreased the propofol-induced relaxation responses (p < 0.05). Propofol (10(-8)-10(-4)M) induced concentration-dependently relaxations in precontracted isolated SO rings by CaCl(2). CONCLUSION: The results suggest that propofol induced concentration-dependent relaxations in precontracted isolated SO rings. These relaxations are independent from NO, cyclooxygenase metabolites, and opened ATP-sensitive and voltage-dependent potassium channels. Opened Ca(2+)-sensitive K(+) channels and inhibited L-type Ca(2+) channels existing in smooth muscle by propofol can contribute to these relaxations. Propofol can be beneficial as alternative drugs for obtaining selective relaxation during SO manometry after controlled clinical studies.

Effect of hypothyroidism on the NO/cGMP pathway of corpus cavernosum in rabbits.

INTRODUCTION: The incidence of hormonal dysfunction as a cause of impotence remains controversial. However, several recent studies have reported evidence of hormonal abnormalities in 25-35% of impotent men. Hypothyroidism has been reported to occur in 6% of impotent men. There is some evidence suggesting that hypothyroidism may be a cause of impotence. AIM: We aimed to investigate the nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) pathway in hypothyroidism in an experimental rabbit model and compared hypothyroid rabbits with controls to evaluate the possible involvement of the NO/cGMP pathway. METHODS: The study comprised 20 male New Zealand white rabbits. The rabbits were divided into two equal groups. The first group had hypothyroidism induced surgically by thyroidectomy for 6 weeks. The second group underwent a sham operation. RESULTS: There was no significant change in the mean body weight of hypothyroid rabbits and controls. Triiodothyronine and thyroxine levels were significantly lower in hypothyroid rabbits. Plasma thyroid-stimulating hormone and prolactin levels were significantly higher in hypothyroid rabbits. Plasma total calcium and parathormone levels remained in the normal range in both groups. MAIN OUTCOME MEASURES: Papaverine-induced concentration-dependent relaxations were similar in both groups. Carbachol-induced relaxation responses decreased in hypothyroid rabbits. There were significant differences between control and hypothyroid rabbits in frequency-dependent relaxations induced by electrical-field stimulation (EFS). YC-1-induced relaxation responses did not change significantly in hypothyroid rabbits. Concentration-dependent relaxations induced by diethylamine (DEA)/NO were similar in both groups. Amrinone-induced relaxation responses did not change significantly in hypothyroid rabbits. CONCLUSION: Reductions of relaxant responses to EFS and carbachol in hypothyroid rabbits can depend on the decrease of released or synthesized NO from nitrergic nerves and endothelium.

Investigation of the relaxant effects of pinacidil and cromakalim on the sheep sphincter of Oddi.

BACKGROUND/AIMS: ATP-sensitive K+ (KATP) channels play an important role in the regulation of smooth muscle membrane potential. This study was designed to investigate the effects of pinacidil and cromakalim, KATP-sensitive channel activators, on sheep sphincters of Oddi (SO). METHODS: SO rings were mounted in a tissue bath and tested for changes in isometric tension in response to pinacidil (10(-9)-10(-4)M) and cromakalim (10(-9)-10(-4)M) in the presence or absence of glibenclamide (10(-6)M), a blocker of KATP channels. Furthermore, concentration-dependent contraction responses of carbachol were obtained. RESULTS: Carbachol (10(-9)-10(-5)M) induced concentration-dependent contraction responses in the SO rings. Pinacidil (10(-9)-10(-4)M) and cromakalim (10(-9)-10(-4)M) induced concentration-dependent relaxation in isolated SO rings precontracted with carbachol (10(-6)M). At their maximum effects, both pinacidil and cromakalim produced nearly full relaxation. In the presence of glibenclamide, concentration-relaxation curves for pinacidil and cromakalim underwent rightward parallel shifts. There were no significant differences between pEC50 and E(max) values of pinacidil and cromakalim in the absence of glibenclamide (10(-6)M) (p > 0.05), but pEC(50) values of pinacidil and cromakalim in the presence of glibenclamide (10(-6)M) were significantly reduced (p < 0.05). CONCLUSION: These results suggest that the relaxation caused in sheep SO by pinacidil and cromakalim is mediated through the same glibenclamide-sensitive KATP channel. Pinacidil and cromakalim have an equipotent relaxing effect in isolated sheep SO and they can be beneficial as alternative drugs for obtaining selective relaxation during SO manometry after controlled clinical studies.

Agmatine facilitates sympathetic neurotransmission in frog myocardium via an action on alfa 2-adrenergic receptors.

OBJECTIVE: In this study, the effect of agmatine was studied on sympathetic neurotransmission in the frog isolated ventricular strips. METHODS: Ventricular strips were prepared from the heart of the pitched frog. Each strip was mounted vertically in an organ bath. Muscle contractions were recorded isometrically by a force displacement transducer and displayed on a polygraph. RESULTS: Concentration-response relationships to noradrenaline were obtained on contractility of frog ventricular strips evoked by electrical stimulation. The responses of noradrenaline were re-obtained in presence of agmatine (3X10(-4) M). Agmatine was found to be ineffective on contractile responses of noradrenaline in electrically driven ventricular strips of frog heart. Transient additional stimulations (TAS) induced contractions. The contractions induced by TAS were re-obtained in presence of agmatine, idazoxan + agmatine and yohimbine + agmatine. Agmatine significantly increased the positive inotropic responses of TAS. The effect of agmatine on contractile responses of TAS was not changed by idazoxan, indicating that imidazoline receptors have not functions in this response. The effect of agmatine on the contractile responses to TAS was reversed by yohimbine, indicating involvement of alpha2 adrenoceptors in this response. Agmatine did not change the contractile responses of ventricular strips to exogenous noradrenaline, indicating that agmatine does not affect postjunctional adrenoceptors. CONCLUSION: These results suggest that agmatine facilitates sympathetic neurotransmission in frog myocardium via an action on prejunctional alpha2 adrenergic receptors located on sympathetic nerve terminals.