Receptor subtypes mediating spinal cardiovascular effects of angiotensin II in rat using losartan and PD 123319

• Published in: European journal of pharmacology 1997-05, Vol.326 (2), p.139-145
• Main Authors: Park, Patricia D.S, Henry, James L
• Format: Article
• Language: English
• Subjects: Angiotensin; Angiotensin Receptor Antagonists; Animals; Arterial pressure; Biological and medical sciences; Biphenyl Compounds - pharmacology; Blood Pressure - drug effects; Cardiovascular control; Central nervous system; Central neurotransmission. Neuromudulation. Pathways and receptors; Drug Evaluation, Preclinical; Fundamental and applied biological sciences. Psychology; Heart rate; Heart Rate - drug effects; Imidazoles - pharmacology; Injections, Intravenous; Injections, Spinal; Losartan; Male; PD 123319; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Spinal cord; Spinal Cord - drug effects; Tetrazoles - pharmacology; Vertebrates: nervous system and sense organs
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(97)85408-8

It has previously been shown in this laboratory that intrathecal administration of 10 μg of angiotensin II produces an increase in arterial pressure and heart rate. As two receptor subtypes of angiotensin II, termed AT 1 and AT 2, have been identified in central nervous tissue this study examines the effects of selective antagonists on the pressor and cardioacceleratory responses to intrathecal administration of 10 μg of angiotensin II to the ninth thoracic spinal cord. The two non-peptide antagonists were losartan (2- n-butyl-4-chloro-5-hydroxymethyl-1-[(2′-(1 H)-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole), which is selective for the angiotensin AT 1 receptor, and PD 123319 (1-[[4-(dimethylamino)-3-methylphenyl]methyl]-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1 H-imidazo[4,5- c]pyridine-6-carboxylic acid, ditrifluoroacetate, dihydrate), which is selective for the angiotensin AT 2 receptor. Intravenous administration of losartan blocked both pressor and cardioacceleratory effects of angiotensin II. Intrathecal administration of losartan blocked only the pressor effects, raising the possibility that block of the heart rate response was in the periphery. Intrathecal administration of PD 123319 blocked the pressor effect of angiotensin II but had no effect on the cardioacceleratory response. However, by itself the antagonist produced a transient increase in arterial pressure and a slower increase in heart rate. The data support the involvement of the angiotensin AT 1 receptor in mediating the effects of exogenously administered angiotensin II but also indicate a possible role of angiotensin AT 2 receptors at the spinal level.