Enhanced susceptibility to histamine-induced cardiac arrhythmias in spontaneously hypertensive rats.
To clarify mechanisms underlying an enhanced susceptibility to cardiac rhythm disturbances in hypertension and myocardial hypertrophy, we evaluated the vulnerability to histamine-induced arrhythmias of isolated left ventricles from spontaneously hypertensive rats (SHR) and age-matched controls (Wistar-Kyoto rats, WKY). Before drug administration, left ventricle-to-body weight ratios, spontaneous firing rates, and the incidence of arrhythmias (including delayed afterdepolarizations) were significantly increased in SHR ventricles versus WKY. In addition, action potential duration (APD) was prolonged in SHR at all levels of repolarization. In WKY but not SHR hearts, histamine (10(-7)-10(-4) M) increased spontaneous firing rates; the incidence of arrhythmias was increased in all hearts, but the response to histamine was most pronounced and occurred at lower threshold drug levels in SHR. After potentials and triggered activity were observed only in SHR. The H2-receptor blocker cimetidine (10(-5) M) and the Ca2(+)-channel antagonist verapamil (10(-6) M) each attenuated the arrhythmogenic influence of histamine in SHR and WKY preparations. Neither chlorpheniramine nor propranolol had any effect. The enhanced vulnerability to arrhythmogenesis observed in SHR myocardium may reflect elevated intracellular calcium levels, which may in turn be potentiated by local ischemia and/or intracardiac histamine release.
Department of Biological Sciences, Wellesley College, Massachusetts 02181.
J S
JS
Cameron
C R
CR
Swigart
G S
GS
Shin
D
D
Katz
A L
AL
Bassett
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced*; D002927:Cimetidine / Q000494:pharmacology; D004198:Disease Susceptibility; D004347:Drug Interactions; D006632:Histamine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014700:Verapamil / Q000494:pharmacology
D002927:Cimetidine; D006632:Histamine; D014700:Verapamil