Hyperreninemia due to increased renal renin synthesis in BioBreeding Worcester rats.
It is well known that diabetes mellitus is often associated with hypertension. We previously reported the unresponsiveness of renin release to volume depletion with impaired renal prostaglandin E2 synthesis in rats with streptozotocin-induced diabetes. However, we have found that BioBreeding Worcester rats, spontaneously susceptible to diabetes mellitus either before or after the onset of diabetes, showed a pronounced fourfold to ninefold increase in plasma renin activity in comparison with control Wistar rats. Furthermore, these rats developed mild hypertension as high as 134 mm Hg after the age of 90 days. The hyperreninemia responded to 1-week sodium loading or restriction; the blood pressure increased during sodium loading. Oral administration of captopril (30 mg/kg) for 1 week resulted in a large blood pressure decrease (-47.1 +/- 5.9 mm Hg, n = 10) in comparison with controls (-17.0 +/- 4.7 mm Hg, n = 12). Vascular response to angiotensin II was also attenuated. Plasma angiotensin II levels were 5.7-fold higher and associated with a 1.5-fold increase of plasma aldosterone concentration compared with control rats, whereas angiotensinogen-plasma concentrations were lower than in control rats. The renal renin content determined enzymatically or histochemically was more enhanced in BioBreeding Worcester rats than in control rats, but the renal renin messenger RNA levels did not differ. These results suggest that the strain-specific hyperreninemia in BioBreeding Worcester rats might be due to posttranscriptional abnormalities of renal renin synthesis. Further work is needed to elucidate the specific mechanism or mechanisms responsible.
Fourth Department of Medicine, Saitama Medical School, Japan.
S
S
Katayama
A
A
Omoto
Y
Y
Maruno
M
M
Inaba
A
A
Itabashi
S
S
Kawazu
J
J
Ishii
K
K
Komeda
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D003920:Diabetes Mellitus / Q000235:genetics / Q000378:metabolism; D004198:Disease Susceptibility; D006973:Hypertension / Q000097:blood / Q000503:physiopathology; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011913:Rats, Inbred BB / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D011919:Rats, Inbred Strains / Q000378:metabolism*; D012083:Renin / Q000096:biosynthesis* / Q000097:blood; D013194:Staining and Labeling
D012333:RNA, Messenger; D000804:Angiotensin II; D012083:Renin