PERTUSSIS TOXIN-INDUCED ADP-RIBOSYLATION OF INHIBITOR-G PROTEINS ALTERS VAGAL CONTROL OF HEART-RATE IN-VIVO

Prior studies have shown that in vivo systemic administration of pertussis toxin in conscious dogs catalyzes ADP ribosylation of G(i) and G(o) proteins, which attenuates intracellular transduction of muscarinic receptor activation. We tested the hypothesis that this impairment may result in the alteration of the following indexes of cardiac vagal activity: baroreflex sensitivity and heart rate variability. Heart rates during submaximal exercise were also determined. These variables were measured in eight conscious dogs before and 72 hr after pertussis toxin administration. Pertussis toxin significantly reduced (P < 0.001) baroreflex sensitivity (from 18.7 +/- 2.6 to 6.8 +/- 1.4 ms/mmHg), the SD of the mean R-R intervals (from 176 +/- 17 to 61 +/- 7 ms), the mean R-R interval (from 742 +/- 32 to 527 +/- 29 ms), and the coefficient of variance [from 235 +/- 15 to 114 +/- 1 (x1,000)]. The heart rate response to graded submaximal exercise after pertussis toxin was higher (P < 0.001) at each exercise level. In in vitro assay, cardiac tissue samples from pertussis toxin-treated dogs incorporated 10-fold less ADP ribose than what has been described previously. These data prove that the in vivo action of pertussis toxin on cardiac inhibitory G proteins has direct consequences on end-organ cardiac responses to vagal activity. This study quantifies the physiological consequences of pertussis toxin-induced impairment of inhibitory G proteins in conscious animals.