Study of the mechanism of antihypertensive peptides VPP and IPP in spontaneously hypertensive rats by DNA microarray analysis.
Many antihypertensive effects of angiotensin-I-converting enzyme (ACE) inhibitory peptides have been studied in spontaneously hypertensive rats (SHRs) and human, however, the mild actions of these peptides expressed by these consecutive uptakes are still not clear. Here, to understand the in vivo antihypertensive effects of well-characterized two peptides, Val-Pro-Pro (VPP) and Ile-Pro-Pro (IPP), DNA microarray was used to analyze gene expression in SHRs fed these peptides for 5 days. By using an Affymetrix analyzer, gene profiling was performed in a target organ, the aorta, of SHRs after repeated administration of VPP and IPP for 5 days. The changes in gene expression were relatively mild; therefore, among the analyzed genes associated with blood pressure, those that showed changes over +/- 5% as compared to the control group were categorized as the renin angiotensin aldosterone system, vascular function, arachidonic acid system, blood coagulation system, and cytokines and growth factors. Significant and marked differences were detected for the endothelial nitric oxide synthase (eNOS) gene (1.89-fold, P<0.05) and the connexin 40 (gap junction 40) gene (2.81-fold, P<0.05). Administration of VPP and IPP led to a slight increase in the expression of the cyclooxigenase (COX-1) gene and a decrease in the expression of both the nuclear factor kappa B subunit (NF-kappaB) gene for vascular function and the peroxisome proliferator activator receptor gamma (PPARgamma) gene. Taken together, these results suggest that VPP and IPP function as ACE inhibitors in the aorta, where they may have a preventive role in cardiovascular function.
Yamaguchi
Naoya
N
Functional Food and Drink Development Laboratory, Calpis, Fuchinobe, Sagamihara-Shi, Kanagawa, Japan.
Kawaguchi
Kyosuke
K
Yamamoto
Naoyuki
N
D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004727:Endothelium / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D012084:Renin-Angiotensin System / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D009842:Oligopeptides; C489032:isoleucyl-prolyl-proline; D016718:Arachidonic Acid; C489031:valyl-prolyl-proline; D007703:Peptidyl-Dipeptidase A