Role of AT(1) receptors and autonomic nervous system in mediating acute pressor responses to ANG II in anesthetized mice.
Hemodynamic responses to angiotensin II and the role of AT(1) and AT(2) receptors and the autonomic nervous system in mediating acute responses to angiotensin II were investigated in anesthetized CD1 mice. Injections of angiotensin II caused dose-related increases in systemic arterial pressure that were antagonized by candesartan. Pressor responses to angiotensin II were not altered by PD-123,319 in doses up to 25 mg/kg iv. At the lowest dose studied (20 microgram/kg iv), the inhibitory effects of candesartan were competitive, whereas at the highest dose (100 microgram/kg iv) the dose-response curve for angiotensin II was shifted to the right in a nonparallel manner with inhibitory effects that could not be surmounted. The inhibitory effects of candesartan were selective and were similar in animals pretreated with enalaprilat (1 mg/kg iv) to reduce endogenous angiotensin II production. Acute pressor responses to angiotensin II were not altered by propranolol (200 microgram/kg iv), phentolamine (200 microgram/kg iv), or atropine (1 mg/kg iv) but were enhanced by hexamethonium (5 mg/kg iv). Increases in total peripheral resistance induced by angiotensin II were inhibited by the AT(1)-receptor antagonist but were not altered by AT(2)-, alpha-, or beta-receptor antagonists. These results suggest that acute pressor responses to angiotensin II are mediated by AT(1) receptors, are buffered by the baroreceptors, and are not modulated by effects on AT(2) receptors and that activation of the sympathetic nervous system plays little if any role in mediating rapid hemodynamic responses to the peptide in anesthetized CD1 mice.
Bivalacqua
T J
TJ
Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana 70112, USA.
Dalal
A
A
Champion
H C
HC
Kadowitz
P J
PJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000758:Anesthesia; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D001341:Autonomic Nervous System / Q000187:drug effects / Q000502:physiology*; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015773:Enalaprilat / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D010276:Parasympatholytics / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000819:agonists / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D010276:Parasympatholytics; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C073402:PD 123319; D018738:Hexamethonium; D001285:Atropine; D011433:Propranolol; D015773:Enalaprilat; C081643:candesartan; D010646:Phentolamine