Effects of rat sinoaortic denervation on the vagal responsiveness and expression of muscarinic acetylcholine receptors.
We studied heart rate (HR) responses to vagal electrical stimulation (VES) and the expression of muscarinic acetylcholine receptors (mAChRs) in the rat atria 1 day (SADa) and 20 days (SADc) after sinoaortic denervation (SAD). Arterial blood pressure (BP) was recorded in conscious, unrestrained rats and during vagal electrical stimulation of the vagus nerve. In the acute phase, SADa rats had hypertension, tachycardia, and increased blood pressure lability. In the chronic phase, heart rate and blood pressure in SADc rats returned to normal whereas blood pressure lability remained increased. VES produced a frequency-dependent bradycardia that was higher in SADa and SADc groups. Binding experiments with [H] N-methylscopolamine showed that in the chronic phase of SAD mAChRs density (SADc = 412.2 +/- 28.64, SADa = 273.38 +/- 48.37 and CTR = 241.5 +/- 25.35 fmol/mg of protein, P < 0.05) and affinity increased in SADc rats (reduced dissociation constant: SADc = 0.45 +/- 0.05, SADa = 1.01+/-0.26, and CTR = 0.98 +/- 0.12 mM, P < 0.05). Our study provides evidence that vagal hyperresponsiveness coexists with increased sympathetic activity in SADa rats without a concomitant increase in mAChRs density or affinity, suggesting that complex mechanisms might modulate the "accentuated antagonism" observed in the acute SAD phase. However, SADc rats had increased bradycardia to VES, increased affinity, and upregulation of mAChRs in the atria. Our results show that, 20 days after SAD in the rat, functional and cellular adaptations occur in the cardiac parasympathetic efferent pathway that may contribute to other regulatory mechanisms to compensate for cardiovascular changes provoked by baroreceptor arch disruption.
Soares
Pedro Paulo da Silva
PP
Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil, Department of Physiology and Pharmacology, Fluminense Federal University, Rio de Janeiro, Brazil. ppsoares@vm.uff.br
Porto
Catarina Segreti
CS
Abdalla
Fernando Maurício Francis
FM
De La Fuente
Raquel Nitrosi
RN
Moreira
Edson Dias
ED
Krieger
Eduardo Moacyr
EM
Irigoyen
Maria Claudia
MC
D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure; D003714:Denervation; D004558:Electric Stimulation; D006339:Heart Rate; D008297:Male; D019832:N-Methylscopolamine / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000032:analysis*; D014630:Vagus Nerve / Q000502:physiology*
D011976:Receptors, Muscarinic; D019832:N-Methylscopolamine