Role of different types of potassium channels in the antidepressant-like effect of agmatine in the mouse forced swimming test.

The administration of agmatine elicits an antidepressant-like effect in the mouse forced swimming test by a mechanism dependent on the inhibition of the NMDA receptors and the L-arginine-nitric oxide (NO) pathway. Since it has been reported that the NO can activate different types of potassium (K(+)) channels in several tissues, the present study investigates the possibility of synergistic interactions between different types of K(+) channel inhibitors and agmatine in the forced swimming test. Treatment of mice by i.c.v. route with subeffective doses of tetraethylammonium (a non specific inhibitor of K(+) channels, 25 pg/site), glibenclamide (an ATP-sensitive K(+) channels inhibitor, 0.5 pg/site), charybdotoxin (a large- and intermediate-conductance calcium-activated K(+) channel inhibitor, 25 pg/site) or apamin (a small-conductance calcium-activated K(+) channel inhibitor, 10 pg/site), augmented the effect of agmatine (0.001 mg/kg, i.p.) in the forced swimming test. Furthermore, the administration of agmatine and the K(+) channel inhibitors, alone or in combination, did not affect locomotion in the open-field test. Moreover, the reduction in the immobility time elicited by an active dose of agmatine (10 mg/kg, i.p.) in the forced swimming test was prevented by the pre-treatment of mice with the K(+) channel openers cromakalim (10 microg/site, i.c.v.) and minoxidil (10 microg/site, i.c.v.), without affecting locomotion. Together these data raise the possibility that the antidepressant-like effect of agmatine in the forced swimming test is related to its modulatory effects on neuronal excitability, via inhibition of K(+) channels.

Salt-induced hypertension in rats alters the response of isolated aortic rings to cromakalim.

The effect of cromakalim, an opener of ATP-sensitive potassium (KATP) channel, on precontracted aortic rings from control and salt-loaded rats was studied in Sprague-Dawley rats. Salt-loading experiments involved the induction of hypertension by 6-week feeding of 80 g sodium chloride (NaCl) per kilogram (kg) diet while the control diet had 3 g NaCl per kg diet. Blood pressure and heart rate were determined by cannulation of a femoral artery under urethane/alpha-chloralose anaesthesia. Isolated aortic rings were mounted in tissue baths for isometric tension measurement. The sodium-potassium adenosine triphosphatase (Na-K ATPase) pump activity was measured by potassium (K+)-induced relaxation (with or without ouabain) following precontraction with 10(-7) M noradrenaline. The KATP channel was studied by measuring the relaxation response to cromakalim, precontracted with either 10(-7) M noradrenaline or 60 mM potassium chloride (KCl). The Na-K ATPase pump appeared to be inhibited during salt loading. ATPase inactivation was found to be ouabain sensitive but did not seem to affect subsequent K(+)-induced contraction. Cromakalim produced relaxation of noradrenaline-precontracted rings from the control rats; rings from salt-loaded rats showed significantly less relaxation than control (p < 0.05) under similar conditions. During K(+)-induced precontraction, cromakalim produced a weak biphasic response in the control rings--an initial relaxation and then a reversal. Cromakalim produced further contraction of K(+)-induced precontraction in the salt-loaded group. The results suggest that ATP-sensitive potassium channels and Na-K ATPase pumps on the vascular smooth muscle membrane may be deactivated in the development of hypertension during salt loading.

Salt-Induced hypertension in rats alters the response of isolated aortic rings to cromakalim

The effect of cromakalim, an opener of ATP-sensitive potassium (K atp) channel, on precontracted aortic rings from control and salt-loaded rats was studied in spague-Dawley rats. Salt-loading experiments involved the induction of hypertension by 6-week feeding of 80 g sodium chloride(NaCl)per kilogram(kg) diet while the control diet had 3 g NaCl per kg diet. Blood pressure and heart rate were determined by cannulation of a femoral artery under urethane/a-chloralose anaesthesia. Isolated aortic rings were mounted in tissue baths for isometric tension measurement. The sodium-potassium adenosine triphosphstase (Na-KATPase) pump activity was measured by potassium(K)-induced relaxation (with or without ouabain) following precontraction with 10-7 M noradrenaline.The KATP channel was studied by measuring the relaxation response to cromakalim,precontracted with either 10-7M noradrenalineor 60mM potassiumchloride(KCl). The Na- k ATPase pump appeared to be inhibited during salt loading. ATPase inactivation was found to be ouabain sensitive but did not seem to affect subsequent K - induced contraction. Cromakalim produced relaxation of noradrenaline precontracted rings frem the control rats; rings from salt-loaded rats showed significantly less relaxtion than control(p<0.05) under similar conditions. During K-induced precontraction, cromakalim produced a weak biphasic response in the control rings-an initial relaxation and then a reversal. Cromakalim produced further contraction of K-induced precontraction in salt-loaded group. The results suggest that ATP-sensitive potassium channels and Na-K ATPase pumps on the vascular smooth muscle membrane may be deactivated in the development of hypertension during salt loading.(AU)