Hydralazine-induced vasodilation involves opening of high conductance Ca2+-activated K+ channels.
The purpose of this study was to investigate whether high conductance Ca2+-activated K+ channels (BK(Ca)) are mediating the vasodilator action of hydralazine. In isolated porcine coronary arteries, hydralazine (1-300 microM), like the K+ channel opener levcromakalim, preferentially relaxed contractions induced by K+ (20 mM) compared with K+ (80 mM). In addition, concentration-relaxation curves for hydralazine (pD2 = 5.38 +/- 0.06; Emax = 85.9 +/- 3.6%) were shifted 10-fold to the right by the BK(Ca) blockers tetraethylammonium (1 mM) and iberiotoxin (0.1 microM). In contrast, nimodipine (a Ca2+-entry blocker), relaxed contractions induced by K+ (20 mM) and K+ (80 mM) equally and nimodipine-induced relaxations were neither antagonized by tetraethylammonium nor by iberiotoxin. In isolated perfused rat hearts, hydralazine (1 microM) increased coronary flow by 28.8 +/- 2.7%. Iberiotoxin (0.1 microM) suppressed this response by 82% (P < 0.05). In conscious, chronically catheterized rats the hypotensive response to hydralazine (0.6 mg kg(-1) min(-1)) was significantly reduced by 41% during infusion of iberiotoxin (0.1 mg kg(-1)). It is concluded, that opening of BK(Ca) takes part in the mechanism whereby hydralazine produces vasodilation.
Bang
L
L
Department of Medicine B 2142, Rigshospitalet, University of Copenhagen, Denmark.
Nielsen-Kudsk
J E
JE
Gruhn
N
N
Trautner
S
S
Theilgaard
S A
SA
Olesen
S P
SP
Boesgaard
S
S
Aldershvile
J
J
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D002273:Carcinogens / Q000494:pharmacology*; D002417:Cattle; D003243:Consciousness; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D019806:Cromakalim / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006834:Hydrazines / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009553:Nimodipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D013552:Swine; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D002273:Carcinogens; D006834:Hydrazines; D010455:Peptides; D015221:Potassium Channels; D014665:Vasodilator Agents; D019806:Cromakalim; C029424:hydrazine; D009553:Nimodipine; D019789:Tetraethylammonium; C064719:iberiotoxin; D011188:Potassium; D002118:Calcium