Different effects of histamine H1 and H2 stimulation on left ventricular contractility in pigs.
Histamine decreases ventricular contractility in some settings but increases it in others. To better understand these apparently discrepant results, we measured hemodynamics and left ventricular pressure (Millar catheter) and volume (ultrasonic crystals) in atrially paced, alpha- and beta-antagonist-treated pigs. Histamine was infused (0.5-10 micrograms.kg-1.min-1) before and after H2-antagonist (ranitidine) pretreatment. Changes in left ventricular contractile function were measured as shift of the end-systolic pressure-volume relationship (delta ESPVR) at a pressure of 100 mmHg. We found that at low doses (0.5 and 1 micrograms.kg-1.min-1), histamine significantly decreased delta ESPVR (-1.1 +/- 1.4 ml, P < 0.05) after H2-antagonist pretreatment. At doses above 1 micrograms.kg-1.min-1, histamine increased contractility in a dose-response fashion [maximum effect: 5.1 +/- 3.3 ml, dose resulting in 50% effect (ED50): 0.75 +/- 1.79 micrograms.kg-1.min-1] that was best described using a Hill coefficient of 2. Ranitidine increased the ED50 by approximately one order of magnitude (0.75 +/- 1.79 to 9.50 +/- 2.60 micrograms.kg-1.min-1, P < 0.05). We conclude that in vivo, at higher doses, histamine increases left ventricular contractility via H2-receptor stimulation, whereas at low doses histamine decreases left ventricular contractility, probably via H1-receptor stimulation.
Cooper
D J
DJ
Pulmonary Research Laboratory, St. Paul's Hospital, University of British Columbia, Vancouver, Canada.
Schellenberg
R R
RR
Walley
K R
KR
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006439:Hemodynamics / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D011312:Pressure; D011899:Ranitidine / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000502:physiology*; D011970:Receptors, Histamine H2 / Q000502:physiology*; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D016277:Ventricular Function, Left / Q000187:drug effects
D006635:Histamine H2 Antagonists; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D006632:Histamine; D011899:Ranitidine