Endogenous angiotensin II suppresses stretch-induced ANP secretion via AT1 receptor pathway.
Angiotensin II (Ang II) is released by stretch of cardiac myocytes and has paracrine and autocrine effects on cardiac myocytes and fibroblasts. However, the direct effect of Ang II on the secretion of atrial natriuretic peptide (ANP) is unclear. The aim of the present study is to test whether Ang II affects stretch-induced ANP secretion. The isolated perfused beating atria were used from control and two-kidney one-clip hypertensive (2K1C) rats. The volume load was achieved by elevating the height of outflow catheter connected with isolated atria from 5cmH(2)O to 7.5cmH(2)O. Atrial stretch by volume load caused increases in atrial contractility by 60% and in ANP secretion by 100%. Ang II suppressed stretch-induced ANP secretion and tended to increase atrial contractility whereas losartan stimulated stretch-induced ANP secretion. Neither PD123319 nor A779 had direct effect on stretch-induced ANP secretion. The suppressive effect of Ang II on stretch-induced ANP secretion was blocked by the pretreatment of losartan but not by the pretreatment of PD123319 or A779. In hypertrophied atria from 2K1C rats, stretch-induced ANP concentration attenuated and atrial contractility augmented. The response of stretch-induced ANP secretion to Ang II and losartan augmented. The expression of AT1 receptor protein and mRNA increased but AT2 and Mas receptor mRNA did not change in 2K1C rat atria. Therefore, we suggest that Ang II generated endogenously by atrial stretch suppresses stretch-induced ANP secretion through the AT1 receptor and alteration of Ang II effect in 2K1C rat may be due to upregulation of AT1 receptor.
Department of Physiology, Chonbuk National University Medical School, Jeonju, Republic of Korea.
Young-Bin
YB
Oh
Shan
S
Gao
Amin
A
Shah
Jong Hun
JH
Kim
Woo Hyun
WH
Park
Suhn Hee
SH
Kim
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002312:Cardiomyopathy, Hypertrophic / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D006977:Hypertension, Renal / Q000150:complications; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010477:Perfusion; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism*; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D012026:Reflex, Stretch / Q000187:drug effects / Q000502:physiology*
C092006:7-Ala-angiotensin (1-7); D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D010446:Peptide Fragments; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; C073402:PD 123319; D009320:Atrial Natriuretic Factor; D019808:Losartan