Comparision of secretagogue effects of rosiglitazone and telmisartan on ANP secretion in rats.
Peroxisome proliferator-activated receptor-gamma (PPAR-γ), a nuclear transcription factor, is a key regulator of insulin signaling, and glucose and fat metabolism. In this study, we evaluated the direct effect of PPAR-γ ligand on the secretion of atrial natriuretic peptide (ANP). The isolated perfused beating atria were used and rosiglitazone (0.01, 0.3 and 1 μM) or telmisartan was perfused into atria with and without inhibitors. High frequency stimulation caused a decreased atrial contractility by 40% and an increased ANP secretion by 80%. Rosiglitazone augmented high frequency-induced ANP secretion and concentration in a dose-dependent manner. Rosiglitazone-induced ANP secretion was attenuated by the pretreatment with PPAR-γ antagonist (GW 9662), or inhibitor for phosphoinositol 3-kinase (PI3-kinase, wortmannin), Akt (API-2) or nitric oxide synthase (l-NAME). Telmisartan, a partial agonist of PPAR-γ with angiotensin II type 1 receptor (AT1R) blocker, also stimulated ANP secretion, which was more potent than rosiglitazone or losartan. Infusion of rosiglitazone or telmisartan in anesthetized rats tended to decrease mean arterial pressure and to increase pulse pressure without difference. A plasma ANP level was increased by telmisartan more than by rosiglitazone. In diabetic rats, an increased plasma ANP level was more prominent than sham rats. Therefore, we suggest that rosiglitazone stimulates high frequency-induced ANP secretion through the PPAR-γ receptor-PI3-kinase-Akt-eNOS pathway and telmisartan shows synergistic effect on ANP secretion.
Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea; Department of Pharmacology, Taishan Medical University, Shandong, China.
Shan
S
Gao
Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Byung Mun
BM
Park
Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Seung Ah
SA
Cha
Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Sung Zoo
SZ
Kim
Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea. Electronic address: shkim@chonbuk.ac.kr.
Suhn Hee
SH
Kim
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001562:Benzimidazoles / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077154:Rosiglitazone; D000077333:Telmisartan; D045162:Thiazolidinediones / Q000494:pharmacology*
D001562:Benzimidazoles; D001565:Benzoates; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D009320:Atrial Natriuretic Factor; D000077333:Telmisartan
Atrial natriuretic peptide; PPAR-γ receptor; Receptor; Rosiglitazone; Telmisartan