Stimulation of angiotensin subtype 2 receptor reduces basal cGMP levels in the neointima of rat aorta after balloon injury.
1. The association between the stimulation of the angiotensin subtype 2 receptor (AT2-R) and the change in tissue levels of cyclic nucleotide was assessed on neointima formation in rat aorta following aortic balloon injury. 2. Tissue levels of guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate levels (cAMP) in the injured and uninjured aorta was determined by enzyme immunoassay at baseline and again 30 s after administration of 10(-7) M angiotension II. 3. Injured and uninjured aorta showed no difference in basal levels of cGMP. Angiotension II reduced the basal level of cGMP in the injured aorta only. 4. This decrease was blocked by a selective AT2-R antagonist (PD123319) and by a nonselective angiotensin II antagonist (angiotensin II antipeptide), but not by a selective angiotensin subtype 1 antagonist (CV-11974). 5. Stimulation with a selective AT2-R caused no change in the level of cAMP in the injured or uninjured aorta. 6. Results suggest that stimulation of AT2-R in proliferative neointima leads to a decreased tissue level of cGMP.
Moroi
M
M
Third Department of Internal Medicine, Toho University School of Medicine, Ohashi Hospital, Tokyo, Japan.
Fukazawa
M
M
Ishikawa
M
M
Aikawa
J
J
Namiki
A
A
Yamaguchi
T
T
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001013:Aorta, Thoracic / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D002404:Catheterization / Q000009:adverse effects; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism* / Q000473:pathology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D000242:Cyclic AMP; D006152:Cyclic GMP; C081643:candesartan