VAGAL RELEASE OF VASOACTIVE-INTESTINAL-PEPTIDE CAN PROMOTE VAGOTONIC TACHYCARDIA IN THE ISOLATED INNERVATED RAT-HEART

Objective: The aim was to determine the extent to which endogenous rel ease of vasoactive intestinal polypeptide (VIP) might be implicated in the modulation of sinoatrial rate in the presence and absence of musc arinic blockade or beta blockade. Methods: Langendorff perfused rat he arts were studied with the right vagus intact. The hearts were maintai ned in sinus rhythm and subjected to right vagal stimuli of 5: IO, 20, and 30 Hz. Results: Administration of exogenous VIP, 10(-8) M, increa sed sinus rate by 20% (p<0.05). This increase in heart rate was reduce d significantly to 8% by the VIP antagonist [D-p-Cl-Phe(6), Leu(17)]VI P. 10(-7) M, which alone had no effect on sinus rate. Vagal stimulatio n reduced sinus rate from a control of 254(SEM 2) to 164(17) beats.min (-1) (p<0.05) at 20 Hz. VIP, 10(-8) M, increased these rates to 284(6) and 220(21) beats.min(-1) (p<0.05). In another eight vagally stimulat ed hearts, frequencies of 5-20 Hz reduced sinus rate. At 30 Hz heart r ate increased in five, and the resultant rate was significantly faster in these [154(10) beats.min(-1)] than in the remainder [98(12) beats. min(-1), p<0.05]. Vagal stimulation also increased sinus rate (p<0.05) in four of seven additional hearts perfused with atropine, 2x10(-6) M . This increase was completely abolished by [D-p-Cl-Phe(6), Leu(17)]VI P. That the effect was not beta adrenergic was demonstrated in eight e xperiments using atropine plus propranolol, 1x10(-7) M. A vagally indu ced increment in rate still occurred (p<0.05) and was abolished by [D- p-CL-Phe(6), Leu(17)]VIP. The ability to ascribe a rate change to VIP release was maximal in the presence of propranolol and atropine, inter mediate in the presence of atropine alone, and minimal in the absence of muscarinic or beta blockade. Conclusions: Vagally released VIP is c apable of limiting the decrement in sinus rate that occurs at high fre quencies of vagal stimulation, and in some circumstances can actually increment sinus rate. Its role as an endogenous modulator of vagal eff ects on heart rate and as a possible cause of vagal and postvagal tach ycardias should be further explored.