Effect of chronic blockade of angiotensin II-receptor subtypes on aortic compliance in rats with myocardial infarction.
This study was undertaken to investigate changes in aortic geometry and compliance after long-term blockade of angiotensin receptors type 1 (AT1) and AT2 receptors under basal conditions and after myocardial infarction (MI). Sham-operated (sham) or MI rats received either no treatment, AT1 antagonist GR138950C (GR; 2 mg/kg/day i.v.), or AT2 antagonist PD123319 (PD; 3 mg/kg/day s.c.). After 3 weeks, mean arterial blood pressure (MAP) was measured. Thoracic aorta diastolic diameter (D[dia]), compliance coefficient (CC), and distensibility coefficient (DC) were determined noninvasively in anesthetized rats by using ultrasound and wall tracking. After the rats were killed, histologic measurements were made on aortic cross sections. In sham rats, MAP was reduced by GR treatment (76 +/- 6 vs. 106 +/- 5 mm Hg), but not by PD. D(dia) was reduced in both GR-treated (1.74 +/- 0.08 vs. 2.09 +/- 0.05 mm) and PD-treated (1.83 +/- 0.05 vs. 2.09 +/- 0.05 mm) sham rats. CC and DC were not modified by either treatment. Although media cross-sectional area was not affected by either GR or PD treatment in sham rats, media thickness and media/lumen ratio were increased in both cases. Induction of MI had no effect on aortic structure, geometry, or mechanics; however, treatment with either GR or PD improved DC versus untreated MI rats. We conclude that AT1 and AT2 receptors are involved in angiotensin II-mediated effects on aortic geometry and mechanics under both basal conditions and after MI. Whereas blockade of AT1 receptors most likely influences vascular properties through a depressor mechanism, AT2 receptors induce pressure-independent remodeling.
Ceiler
D L
DL
Department of Pharmacology, Cardiovascular Research Institute Maastricht, Maastricht University, The Netherlands.
Nelissen-Vrancken
H J
HJ
De Mey
J G
JG
Smits
J F
JF
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D001572:Benzofurans / Q000008:administration & dosage / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D007093:Imidazoles / Q000008:administration & dosage / Q000627:therapeutic use; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D011725:Pyridines / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014463:Ultrasonography
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001572:Benzofurans; D007093:Imidazoles; D011725:Pyridines; C073402:PD 123319; C089586:saprisartan potassium