Effect of histamine on isolated working guinea pig heart with left ventricular hypertrophy produced by pressure overload

Left ventricular hypertrophy in guinea pigs was produced by partial constriction of the ascending aorta. 65-70 d after surgery, the animals were sacrificed and the hearts were mounted on a working heart apparatus. Results showed that all parameters of cardiac function in the hypertrophied (HT) group were depressed. The dose-response (D-R) curves for histamine (H) in the HT group shifted leftward and upward as compared with the sham-operated (S) group. In the presence of pyrilamine (P), the D-R curves for H shifted to the left in the S group, but the curves shifted to the right in the HT group. In the presence of cimetidine (C), the D-R curves for H shifted downward and rightward in both groups. In contrast to H, the D-R curves for norepinephrine (NE) on LVP/HW and CBF/HW in the HT group shifted rightward and downward as compared with the S group. These results indicate that the sensitivity of H2 receptors in hypertrophied heart was increased and that of beta receptors was slightly decreased, suggesting a possible beneficial effect of H2 receptor agonists in the treatment of certain types of cardiac failure, which are insensitive to catecholamine stimulation.