The effect of pH on rabbit atrial response to histamine

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Abstract
The chronotropic response of isolated rabbit atria in normal Tyrode's medium increases monotonically with increasing doses of histamine (9 × 10−7–9 × 10−4 M). Plots of the inverse of response against the inverse of concentration were linear; and from these plots were derived values for the theoretical maximum response at 'infinite' dose and for the histamine concentration required to evoke a half maximum response. Alteration of pH by changing [HCO3−] at constant pCO2, [Na+] and osmolality did not appreciably affect the response to histamine in the range pH 7.0–7.6. However, at pH below 7.0 the magnitude of histamine response was reduced at all concentrations of histamine tested. In the pH range 7.0–7.6, additions of NaHCO3 at constant pCO2 increased the spontaneous rate of rabbit atria (in the absence of histamine); however, there was little effect of changing pH (in this range) by altering [HCO3−] at constant pCO2 when [Na+] and osmolality were kept constant. Immersion in solutions at pH's less than 7.0 led to decline in spontaneous rate and force of contraction. It is probable that depression of adenyl cyclase activity rather than a specific change in ionization of histamine receptor is responsible for a decreased response to histamine at pH 6.9.