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

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...

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Main Authors: Taeko Hata, Yoshinori Funakami, Eiji Itoh
Format: Article
Language:English
Published: Elsevier 2005-01-01
Series:Journal of Pharmacological Sciences
Online Access:http://www.sciencedirect.com/science/article/pii/S1347861319322509
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author Taeko Hata
Yoshinori Funakami
Eiji Itoh
author_facet Taeko Hata
Yoshinori Funakami
Eiji Itoh
author_sort Taeko Hata
collection DOAJ
description 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
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spelling doaj.art-db9618bf8235468492585fb69fc12f902022-12-22T03:04:25ZengElsevierJournal of Pharmacological Sciences1347-86132005-01-01973386392Effects of AF-DX116 and Other Muscarinic Receptor Antagonists on Orthostatic Hypotension in Autonomic Imbalanced (SART-Stressed) RatsTaeko Hata0Yoshinori Funakami1Eiji Itoh2Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, Japan; Corresponding author. FAX: +81-6-6721-2353 E-mail: hata_t@phar.kindai.ac.jpDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, JapanDepartment of Pharmacology, Faculty of Pharmaceutical Sciences, Kinki University, 3-4-1 Kowakae, Higashi-Osaka 577-8502, JapanSART (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 tilthttp://www.sciencedirect.com/science/article/pii/S1347861319322509
spellingShingle Taeko Hata
Yoshinori Funakami
Eiji Itoh
Effects of AF-DX116 and Other Muscarinic Receptor Antagonists on Orthostatic Hypotension in Autonomic Imbalanced (SART-Stressed) Rats
Journal of Pharmacological Sciences
title Effects of AF-DX116 and Other Muscarinic Receptor Antagonists on Orthostatic Hypotension in Autonomic Imbalanced (SART-Stressed) Rats
title_full Effects of AF-DX116 and Other Muscarinic Receptor Antagonists on Orthostatic Hypotension in Autonomic Imbalanced (SART-Stressed) Rats
title_fullStr Effects of AF-DX116 and Other Muscarinic Receptor Antagonists on Orthostatic Hypotension in Autonomic Imbalanced (SART-Stressed) Rats
title_full_unstemmed Effects of AF-DX116 and Other Muscarinic Receptor Antagonists on Orthostatic Hypotension in Autonomic Imbalanced (SART-Stressed) Rats
title_short Effects of AF-DX116 and Other Muscarinic Receptor Antagonists on Orthostatic Hypotension in Autonomic Imbalanced (SART-Stressed) Rats
title_sort effects of af dx116 and other muscarinic receptor antagonists on orthostatic hypotension in autonomic imbalanced sart stressed rats
url http://www.sciencedirect.com/science/article/pii/S1347861319322509
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