ABSTRACT
The influence of glibenclamide(GBC), a blocker of ATP-sensitive K+ channells, on relaxation caused by cromakalin(CKL), acetylcholine (ACh) and iloprost (ILO) was assessed in aortic rings (AR) with (E+) or without endotheliium (E-) and in the perfused arterial mesentery (MES) of the rat. In AR preconstricted with noradrenaline, CKL(0.03-10 *M) and ILO (5.5 nM) caused graded vasodilations which were not modified by endothelium removal. ACh(0.01-3 *M) only relaxed E+AR preparations. GBC (3*M) markedly reduced responses to CKL in E+AR and E-AR, but did not affect vasodilation induceds by ILO in E-AR and by ACH in E+AR. In MES preconstricted with methoxamine, bolus injections of CKL (10 or 30 nmol) or ACh (0.03-1nmol) caused graded reductions of perfusion pressure. Only the responses to CKL were significantly inhibited by GBC (10 *M). We conclude that AR and MES contain functional ATP-sensitive K+ channels, which, however, do not play a significant role in the endothelium-dependent vasodilation triggered by ACh or in the endothelium-indipendent relaxation induced by ILO
Subject(s)
Animals , Rats , Male , Acetylcholine/pharmacology , Adenosine Triphosphate/antagonists & inhibitors , Endothelium, Vascular/drug effects , Glyburide/pharmacology , Iloprost/pharmacology , Potassium Channels/drug effects , Vasodilation/drug effects , Adenosine Triphosphate/metabolism , Aorta, Thoracic/drug effects , Benzopyrans/pharmacology , Electric Stimulation , Mesenteric Arteries/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth, Vascular/drug effects , Potassium Channels/metabolism , Pyrroles/pharmacology , Rats, Inbred StrainsABSTRACT
1. The present study assesses the influence of tolerance to, and dependence on morphine on the availability of Ca2+ for contraction of the mouse isolated vas deferens induced by noradrenaline (NA). 2. Reducing Ca2+ content in the bathing solution from 2.5 to 1.2 or 0.6 mM significantly reduced the magnitude of NA-induced contractions. This effect was similar in preparations obtained form control and tolerant/dependent mice (P > 0.05 at any Ca2+ concentration). 3. Omission of Ca2+ from the bathing solution caused a rapid and similar loss of responsiveness to a macimally effective concentration of NA (300 micronM) in both groups (t1/2 < 3 min, P > 0.05). 4. Vasa deferentia obtained from control and tolerant/dependent mice were equally sysceptible to non-competitive antagonism of NA-induced contraction by verapamil (3 to 30 micronM; pD2' values of 5.50 and 5.26, rspectively, (P > 0.05 at any concentration of verapamil). 5. Preparations from tolerant/dependent mice displalyed significant supersensitivity to NA, the magnitude of which was not influence by modifying the Ca2+ concentration in the bathing medium (2.6-and 1.7-fold in 0.6 and 2.5mMCa2+, respectively, P < 0.05. 6. I conclude that tolerance to and dependence on morphine are not associated with changes in the availability of Ca2+ for NA-induced contractions of the mouse vas deferens
Subject(s)
Mice , Animals , Male , Calcium/metabolism , Morphine/pharmacology , Norepinephrine/pharmacology , Vas Deferens/drug effects , Drug Tolerance , Muscle Contraction/drug effectsABSTRACT
The current study assesses the influence of the N-methil-D-aspartate (NMDA) receptor antagonist D-2-amino-7-phosphonohepatanoate (AP7) on the pressor effect of glutamate microinjected into the dorsal periaqueductal gray matter (DPAG) of urethane-anesthetized rats. Glutamate (20, 40 and 80 nmol/site) caused dose-related reproducible increases in systolic and diastolic blood pressure. Microinjection of saline into the DPAG did not alter the pressor effects of glutamate (80 nmol/site). Similar pretreatment with AP7 (2nmol/site) significantly (P < 0.05) attenuated the pressor effects of glutamate from ñ26.5 ñ 7.0 to +3.4 ñ 3.3 mmHg (sistolic blood pressure). We conclude that the pressor efffect of glutamate in the DPAG is mediated largely by activation of NMDA receptors