The mechanism of distinct diurnal variations of renin-angiotensin system in aorta and heart of spontaneously hypertensive rats.
Diurnal variations in plasminogen activator inhibitor-1 mRNA expression are different between the spontaneously hypertensive rats (SHRs) and the Wistar-Kyoto (WKY) rats, and between the aorta and the heart. To elucidate the mechanisms, we examined diurnal changes in the circulating renin-angiotensin system in the SHR and WKY rats. Diurnal variations in plasma renin activity (PRA), plasma angiotensin I, and aldosterone concentrations were similar between the SHR and WKY rats. On the other hand, plasma angiotensin II (Ang II) concentration in the SHR was lower than that in the WKY rats at most time points, but increased to the level of the WKY rats in the late light phase. Treatment with AT1 receptor antagonist candesartan increased plasma Ang II concentration except at ZT 8 and lessened its diurnal variation in the SHR. At the peak in plasma Ang II in the SHR, Ang II regulated genes such as transforming growth factor-beta1 and p22phox were upregulated in the aorta. On the other hand, these genes were upregulated throughout the day in the heart of SHR. Candesartan treatment increased AT1a receptor mRNA expression in the heart but not in the aorta of SHR. These findings suggest that an AT1 receptor-mediated mechanism might cause a surge in plasma Ang II concentration at the late light phase in the SHR. Homologous down-regulation of AT1a receptor by Ang II may dampen the effect of a surge in plasma Ang II concentration in the heart of SHR.
Naito
Yoshiro
Y
Department of Internal Medicine, Cardiovascular Division, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Japan.
Tsujino
Takeshi
T
Matsumoto
Mika
M
Okuda
Satoshi
S
Sakoda
Tsuyoshi
T
Ohyanagi
Mitsumasa
M
Masuyama
Tohru
T
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D002940:Circadian Rhythm; D015536:Down-Regulation; D005819:Genetic Markers; D008297:Male; D009206:Myocardium / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000187:drug effects*; D015842:Serine Proteinase Inhibitors / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D005819:Genetic Markers; D017395:Plasminogen Activator Inhibitor 1; D015842:Serine Proteinase Inhibitors; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D019255:NADPH Oxidases; C515768:Cyba protein, rat; C081643:candesartan