Decrease in circulating and urine adrenomedullin concentrations in stroke-prone spontaneously hypertensive rats.
Adrenomedullin (AM) is a peptide with potent vasodilatory and hypotensive properties. Plasma AM levels in rats with experimentally induced hypertension, such as Dahl salt-sensitive rats and two-kidney, one-clip hypertensive rats, are higher than those in normotensive rats. We previously noted, however, that plasma AM levels in spontaneously hypertensive rats (SHR) are similar to those in Wistar-Kyoto rats. To define the role of AM in rats with severe hypertension, we investigated changes in circulating and tissue AM levels in stroke-prone spontaneously hypertensive rats (SHRSP/Izm). The immunoreactive rat AM levels in plasma, urine, and tissue measured with a sensitive radioimmunoassay, and the AM mRNA levels in various tissues in 15-wk-old SHRSP/Izm were compared with those in age-matched Wistar-Kyoto rats (WKY/Izm). The plasma and urinary AM levels in SHRSP/Izm were significantly lower than those in WKY/Izm [plasma AM, 2.14+/-0.06 (SE) vs. 3.24+/-0.16 fmol/ml, p< 0.001; urinary AM, 16.36+/-3.21 vs. 36.12+/-6.09 fmol/ml, p< 0.01]. A negative correlation was found between the plasma AM level and the systolic blood pressure in both SHRSP/Izm and WKY/Izm. Reverse-phase high-performance liquid chromatography showed that the molecular components of plasma immunoreactive AM in SHRSP/Izm were similar to those in WKY/Izm. Furthermore, tissue AM levels in various organs in SHRSP/Izm were not lower than those in WKY/Izm. In conclusion, low levels of circulating AM may contribute to the maintenance of high blood pressure in 15-wk-old SHRSP/Izm. These low plasma AM levels may be caused by accelerated metabolism of circulating AM in SHRSP/Izm.
Hirano
S
S
First Department of Internal Medicine, Miyazaki Medical College, Japan.
Ishiyama
Y
Y
Matsuo
T
T
Imamura
T
T
Sakata
J
J
Kitamura
K
K
Koiwaya
Y
Y
Eto
T
T
D053607:Adrenomedullin; D000367:Age Factors; D000419:Albuminuria; D000818:Animals; D000959:Antihypertensive Agents / Q000097:blood* / Q000652:urine*; D001794:Blood Pressure; D001835:Body Weight; D002561:Cerebrovascular Disorders / Q000097:blood; D003401:Creatine / Q000652:urine; D015870:Gene Expression / Q000502:physiology; D006339:Heart Rate; D006973:Hypertension / Q000097:blood; D008297:Male; D010455:Peptides / Q000097:blood* / Q000235:genetics / Q000652:urine*; D012333:RNA, Messenger / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR / Q000097:blood*; D011921:Rats, Inbred WKY
D000959:Antihypertensive Agents; D010455:Peptides; D012333:RNA, Messenger; D053607:Adrenomedullin; D003401:Creatine