Effect of losartan microinjections into the NTS on the cardiovascular components of chemically evoked reflexes in a rabbit model of acute heart ischemia.
In the acute phase of myocardial infarction (MI) there are modifications of the autonomic outflow with an increase in the sympathetic tone and changes in cardiovascular reflexes. Activation of angiotensin AT1 receptors in the nucleus tractus solitarii (NTS) inhibits the baroreceptor and enhances the carotid chemoreflex. In this study, we investigated the role of NTS-AT1 receptors on the cardiovascular reflex responses evoked on stimulation of carotid chemoreflex and cardiac chemosensitive fibres in the acute phase of MI. We also test the hypothesis that changes in cardiovascular responses to activation of carotid chemo and cardiac chemosensitive reflexes are secondary to changes in haemodynamic conditions due to infarction or to the activation of nociceptors of the heart. Rabbits were anaesthetised, paralysed and artificially ventilated. Carotid chemoreceptors and cardiac chemosensitive fibres were stimulated with lobeline and ATP, respectively. Arterial blood pressure, electrocardiogram and heart rate were monitored. A craniotomy was made to expose the caudal portions of the medulla and a multibarreled glass microelectrode was inserted in order to allow the identification of NTS and the microinjection of losartan (an angiotensin AT1 receptor antagonist). The heart was exposed by a midline thoracotomy and cardiac ischemia was produced by ligating the left descending coronary artery. The carotid chemoreflex and cardiac chemosensitive reflexes were evoked before and following the coronary ligation. The effect of losartan injection into the NTS on these reflexes was also assessed. In control experiments reflexes were assessed before and after the administration of capsaicin and procainamide. Results show that the activation of carotid chemoreflex elicited a greater increase of blood pressure and bradycardia after MI and that this was partially reversed by losartan microinjection after MI. Also the stimulation of cardiac chemosensitive fibres evoked a larger decrease on blood pressure and heart rate after MI and these were also partially reversed by losartan. The same enhancement of cardiovascular carotid chemo and cardiac chemosensitive receptors was observed after administration of capsaicin on the ventricular surface but not after procainamide. In conclusion, this study strongly suggests that, at NTS level, angiotensin AT1 receptors are involved in the modifications of autonomic outflow observed in the acute phase of MI.
Rosário
L B
LB
Instituto de Fisiologia da Faculdade de Medicina da Universidade de Lisboa, Av. Prof Egas Moniz, 1649-028 Lisbon, Portugal.
Rocha
Isabel
I
Silva-Carvalho
Luis
L
D000208:Acute Disease; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D002628:Chemoreceptor Cells / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009203:Myocardial Infarction / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D011342:Procainamide / Q000494:pharmacology; D011817:Rabbits; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects / Q000502:physiology; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D017552:Solitary Nucleus / Q000187:drug effects* / Q000503:physiopathology*
D044140:Receptor, Angiotensin, Type 1; D019808:Losartan; D011342:Procainamide; D002211:Capsaicin