Effects of AF-DX116 and Other Muscarinic Receptor Antagonists on Orthostatic Hypotension in Autonomic Imbalanced (SART-Stressed) Rats

Abstract

SART (specific alternation of rhythm in temperature)-stressed rats are an animal model of autonomic imbalance created by exposing animals to repeated cold stress. The SART-stressed rats have been shown to easily develop orthostatic hypotension (OH). In this study, effects of AF-DX116, a selective M2 antagonist, and other muscarinic receptor antagonists on OH were investigated in SART-stressed and unstressed rats. Each anesthetized rat was canulated into the left common carotid artery, and blood pressure (BP) and heart rate were measured. Stimulation for postural change was initiated by head-up tilting. As the indices of OH, the maximum fall of BP, % reflex (recovery from maximum fall), and the area enclosed between the baseline and the recovery curve for BP (AUC) were used. Large AUC and small % reflex in SART-stressed rats were changed, becoming similar to those of the unstressed rats by AF-DX116 and methoctoramine. Atropine and methylatropine had similar effects to AF-DX116. However, the effects of methoctoramine, atropine, and methylatropine were less than that of AF-DX116. Pirenzepine was not effective. In conclusion, it was suggested in SART-stressed rats that OH was related to hyperactivity in the parasympathetic nerve and the M2 receptor played the major role in OH. Keywords:: SART (specific alternation of rhythm in temperature) stress, AF-DX116, orthostatic hypotension, muscarinic receptor, head-up tilt