VASCULAR CONVERSION OF ANGIOTENSIN-I IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE AND WISTAR-KYOTO RATS

Objective: Linkage studies have shown that the gene locus for angioten sin converting enzyme (ACE) is associated with the expression of hyper tension in stroke-prone spontaneously hypertensive rats (SHRSP). We te sted the hypothesis that the conversion of angiotensin I (Ang I) to an giotensin II (Ang II) in blood vessels is elevated in SHRSP. Design: W e measured the conversion rate of Ang I to Ang II during one pass thro ugh an isolated resistance vessel bed. We used the same substrains of SHRSP and Wistar-Kyoto control rats (WKY) that had been employed in th e earlier linkage studies. Methods: Isolated hindquarters from young a nd adult (10- to 12- and 36- to 38-week-old) rats were perfused with a n 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 cha nnels. Conversion and extraction rates were calculated from angiotensi n levels in hindquarter and blank perfusion channels, respectively. Re sults: The conversion rates of Ang I to Ang II did not differ between SHRSP and WKY in young or in adult rats. Captopril completely abolishe d the formation of Ang II in all groups of rats. During infusion at th e higher dose of Ang I, the extraction of Ang I was significantly decr eased in SHRSP compared with WKY. Conclusions: Our results are consist ent 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 i n SHRSP. These findings suggest that other genes close to the ACE locu s or the hyperexpression of the enzyme in other areas may contribute t o hypertension in these rats.