The role of 5-hydroxytryptamine in the control of pulmonary vascular tone in a rabbit model of pulmonary hypertension secondary to left ventricular dysfunction.
The role of 5-hydroxytryptamine (5-HT) in a rabbit model of pulmonary hypertension (PHT) secondary to left ventricular dysfunction was investigated. Following pulmonary artery catheterisation under anaesthesia, 5-HT (1-400 microg kg(-1) i.v.) was administered before and after either 5-HT(2A) receptor antagonism with ketanserin (0.5 mg kg(-1)) or infusion of the nitric oxide synthase inhibitor, l-NAME (30 micromol min(-1)). Eight week coronary artery ligated rabbits demonstrate increased mean pulmonary arterial pressure (PAP) compared to controls (17.0+/-0.5 versus 12.0+/-0.5 mmHg, P<0.001) accompanied by right ventricular hypertrophy. 5-HT alone produced a greater pulmonary pressor response in rabbits with PHT (increase of 7.5+/-1.2, n=12 c.f. 3.5+/-0.4 mmHg in shams, n=12, P<0.01). Ketanserin had no effect on basal PAP in either PHT or control rabbits but inhibited the response to 5-HT in both groups. The response to 5-HT following l-NAME was increased in both groups and was greater in rabbits with PHT (an increase of 20.1+/-2.9, n=6 c.f. 11.4+/-1.8 mmHg, n=6, P<0.05). These results suggest that the difference shown in the in vivo pulmonary response to exogenous 5-HT is mediated largely through 5-HT(2A) receptors in this model. However, activity of endogenous 5-HT at the 5-HT(2A) receptors is not responsible for maintaining the raised basal PAP through vasoconstriction in PHT rabbits once PHT has developed.
Deuchar
Graeme A
GA
Department of Medical Cardiology, Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow G31 2ER, UK. graeme.a.deuchar@clinmed.gla.ac.uk
Hicks
Martin N
MN
MacLean
Margaret R
MR
D000818:Animals; D001011:Aorta; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects; D004195:Disease Models, Animal; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000150:complications / Q000503:physiopathology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000503:physiopathology; D011817:Rabbits; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013318:Stroke Volume / Q000187:drug effects / Q000502:physiology; D018487:Ventricular Dysfunction, Left / Q000150:complications / Q000503:physiopathology*
D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D012701:Serotonin; D007650:Ketanserin; D019331:NG-Nitroarginine Methyl Ester