Vascular conversion of angiotensin I in stroke-prone spontaneously hypertensive and Wistar-Kyoto rats.
OBJECTIVE
Linkage studies have shown that the gene locus for angiotensin converting enzyme (ACE) is associated with the expression of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). We tested the hypothesis that the conversion of angiotensin I (Ang I) to angiotensin II (Ang II) in blood vessels is elevated in SHRSP.


METHODS
We measured the conversion rate of Ang I to Ang II during one pass through an isolated resistance vessel bed. We used the same substrains of SHRSP and Wistar-Kyoto control rats (WKY) that had been employed in the earlier linkage studies.


METHODS
Isolated hindquarters from young and adult (10- to 12- and 36- to 38-week-old) rats were perfused with an artificial medium and then infused with Ang I at 0.5 and 2 pmol/ml. Ang I and II were measured with high-performance liquid chromatography and radioimmunoassay in hindquarter effluent and in blank control channels. Conversion and extraction rates were calculated from angiotensin levels in hindquarter and blank perfusion channels, respectively.


RESULTS
The conversion rates of Ang I to Ang II did not differ between SHRSP and WKY in young or in adult rats. Captopril completely abolished the formation of Ang II in all groups of rats. During infusion at the higher dose of Ang I, the extraction of Ang I was significantly decreased in SHRSP compared with WKY.


CONCLUSIONS
Our results are consistent with the notion that the metabolism of angiotensin is decreased in spontaneously hypertensive rats. However, we found no support for the hypothesis that vascular ACE is responsible for high blood pressure in SHRSP. These findings suggest that other genes close to the ACE locus or the hyperexpression of the enzyme in other areas may contribute to hypertension in these rats.
Hilgers
K F
KF
Department of Medicine-Nephrology, University of Erlangen-Nuremberg, Germany.
Veelken
R
R
Mai
M
M
Ganten
U
U
Ganten
D
D
Luft
F C
FC
Mann
J F
JF
D000375:Aging / Q000097:blood / Q000502:physiology; D000803:Angiotensin I / Q000097:blood*; D000804:Angiotensin II / Q000097:blood*; D000818:Animals; D002561:Cerebrovascular Disorders; D002851:Chromatography, High Pressure Liquid; D006614:Hindlimb / Q000098:blood supply; D006973:Hypertension / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011918:Rats, Inbred SHR / Q000097:blood* / Q000235:genetics* / Q000502:physiology; D011921:Rats, Inbred WKY / Q000097:blood* / Q000502:physiology
D000804:Angiotensin II; D000803:Angiotensin I