title: Role of calcium-dependent K+ channels in the regulation of arterial and venous tone by nitric oxide in pigs.
abstract: Effects of inhibition of calcium-dependent potassium channels (K+Ca channels) on the regulation of arterial and venous tone by nitric oxide (NO) were studied in anaesthetized pigs following vagotomy and blockade of autonomic ganglia. Selective inhibition of K+Ca channels by charybdotoxin (CTX, 2 microg/kg iv) or iberiotoxin (IbTX, 1 microgram/kg) significantly augmented mean total peripheral resistance (TPR) to levels 30-60% above control. Venous and pulmonary vascular tone were assessed by changes in effective compliances of the venous (EVC) and pulmonary (EPC) vascular beds as calculated from changes in central venous and diastolic pulmonary arterial blood pressure during haemorrhagia (-5 ml/kg) and hypervolaemia (+5 ml/kg). Blockade of K+Ca channels significantly decreased both EVC (-20 to -30%) and EPC (-30 to -50%). Both CTX and IbTX significantly diminished the vasodilation caused by the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) both during control conditions and following experimental vasoconstriction induced by systemic inhibition of NO-synthesis by NG-nitro-L-arginine methyl ester (L-NAME) or infusion of vasoconstrictor agonists. Dilator effects of the adenosine 3',5'-cyclic monophosphate (cAMP)-dependent agonist adenosine were only slightly reduced. However, blockade of K+Ca channels did not increase vasoconstriction induced by L-NAME significantly. These results suggest that activation of vascular K+Ca channels is an important mechanism by which NO attenuates the constrictor tone of resistance and capacitance vessels in vivo.
authors.affiliation: I. Physiologisches Institut, Universität Heidelberg, Im Neuenheimer Feld 326, D-69120 Heidelberg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Zanzinger
authors.forename: J
authors.initials: J
authors.lastname: Czachurski
authors.forename: H
authors.initials: H
authors.lastname: Seller
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D001808:Blood Vessels / Q000502:physiology*; D001810:Blood Volume / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002302:Cardiac Output / Q000187:drug effects; D018999:Charybdotoxin / Q000494:pharmacology; D019332:Endothelin-1 / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D026423:S-Nitroso-N-Acetylpenicillamine; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D019332:Endothelin-1; D004791:Enzyme Inhibitors; D015221:Potassium Channels; D014665:Vasodilator Agents; D000804:Angiotensin II; D001127:Arginine Vasopressin; D018999:Charybdotoxin; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine; D002118:Calcium; D009638:Norepinephrine