DIFFERENTIAL REGULATION OF VASCULAR ANGIOTENSIN I-CONVERTING ENZYME IN HYPERTENSION

The angiotensin I-converting enzyme (ACE) gene is found on the locus t hat has been linked to high blood pressure after sodium loading in rat s, so in the present study we investigated the role of vascular ACE fo r the pathophysiology of hypertension in the corresponding parental st rains, Wistar-Kyoto (WKY) rats and stroke-prone spontaneously hyperten sive rats (SHRSP), in basal conditions at different ages and after sod ium loading. Blood pressure was already significantly enhanced in SHRS P from 4 weeks of age, and sodium loading induced an additional increa se only in the hypertensive strain. In the aorta, basal ACE gene expre ssion, analyzed by quantitative polymerase chain reaction, and ACE act ivity were similar in both strains, whereas mRNA levels were elevated in SHRSP after salt compared with WKY rats and correlated with an incr ease in enzymatic activity. In mesenteric arteries, ACE mRNA levels we re significantly enhanced in SHRSP at all ages, although ACE activity was not different between the strains. These results were not modified after sodium loading. These data demonstrate that the level of ACE ac tivity in plasma and vascular tissue can be controlled in a different manner within a rat strain and that in contrast to the soluble form, t he membrane-bound ACE may be the one responsible for determining the v asoactive effects of angiotensin II. In addition, ACE undergoes a diff erent regulation in vascular tissues of SHRSP compared with WKY rats, which might be involved in the regulation of blood pressure in these a nimals.