Augmented diurnal variations of the cardiac renin-angiotensin system in hypertensive rats.
There are several controversies concerning the enhanced gene expression of cardiac renin-angiotensin system components in spontaneously hypertensive rats (SHR) compared with their normotensive control Wistar-Kyoto (WKY) rats. We hypothesized that these discrepancies arise from circadian fluctuations in gene expression. We examined the circadian mRNA expression of renin, angiotensinogen, ACE, and angiotensin type 1a (AT1a) and type 2 (AT2) receptors in the hearts of SHR and WKY rats by real-time quantitative reverse transcription-polymerase chain reaction. The cardiac mRNA expression of the renin-angiotensin system components showed circadian oscillations in both SHR and WKY rats. The amplitudes of these circadian fluctuations were greater in the SHR than in the WKY rats. The mRNA levels of the renin-angiotensin system components were also increased in the SHR compared with the WKY rats at many time points (especially during the dark phase). However, the levels of ACE, AT1a receptor, and AT2 receptor mRNA in the SHR and WKY rats were almost the same during the late light phase. In contrast to mRNA expression, ACE activity was similar both at the time of maximum and minimum mRNA expression. The AT1 receptor antagonist candesartan upregulated AT1a receptor mRNA and downregulated ACE mRNA at specific time points only in the SHR group. Our findings of differential diurnal expression of cardiac renin-angiotensin system genes in SHR and WKY rats appear to explain the discrepancies between prior studies. However, the physiological relevance of the differential circadian mRNA expression of the renin-angiotensin system components remains to be elucidated.
Naito
Yoshiro
Y
Department of Internal Medicine, Cardiovascular Division, Hyogo College of Medicine, Nishinomiya, Japan.
Tsujino
Takeshi
T
Fujioka
Yoshio
Y
Ohyanagi
Mitsumasa
M
Iwasaki
Tadaaki
T
D057911:Angiotensin Receptor Antagonists; D000808:Angiotensinogen / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D002940:Circadian Rhythm / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism; D012083:Renin / Q000235:genetics / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000808:Angiotensinogen; D007703:Peptidyl-Dipeptidase A; D012083:Renin; C081643:candesartan