Normotensive and Hypertensive Rats

We evaluated whether vascular kallikrein is altered in rats with genetic or experimental hypertension. Group 1 was infused intraperitoneally with angiotensin II (Ang II) or vehicle for 4 weeks; group 2 was injected subcutaneously with deoxycorticosterone (75 ^unol/kg once a week) or vehicle for 4 weeks; group 3 consisted of uninephrectomized rats on high sodium intake given deoxycorticosterone or vehicle; and group 4 consisted of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats. Active and total kallikrein activity was measured in abdominal aortic homogenates using an amidolytic assay. Ang II increased systolic blood pressure at a dose of 400 nmol/kg per day (146±6 versus 123±3 mm Hg in controls, P<.01) but not at 80 nmol/kg per day. Deoxycorticosterone did not increase blood pressure except in uninephrectomized rats on high salt (173±6 versus 135±4 mm Hg in controls, P<.01). Blood pressure averaged 194±2 mm Hg in SHR and 123±3 mm Hg in WKY rats. Vascular kallikrein was Glandular kallikrein is a serine protease that releases kinins from kininogen. Kinins, whose vasodilating action is mediated by the release of endothelium-derived relaxing factors and prostacyclin from vascular endothelial cells,' may play an important role in the regulation of systemic blood pressure and regional hemodynamics. In recent years evidence has been provided for the existence of a vascular kallikrein-kinin system in the rat. A kininogenase resembling glandular kallikrein is present in rat arteries and veins. In addition, local synthesis of kallikrein is supported by the presence of specific messenger RNA for kallikrein in the rat vasculature. The observation that in one-kidney, one clip renovascular hypertension kallikrein activity is decreased in the arteries suggests that depressed formation of kinins may contribute to increased vascular resistances. On the other hand, depressed kininogenase activity may be secondary to the increase in blood pressure. At present it is not known whether alteration in vascular kallikrein is a typical feature of one-kidney, one clip hypertension, an experimental model known to be volume dependent, or whether it occurs in other forms of hypertension. Therefore, we designed a study aimed at evaluating whether kallikrein activity is altered in the abdominal aorta of spontaneously hypertensive rats (SHR), rats given a chronic infusion of pressor or nonpressor doses of angiotensin II (Ang II), and deoxycorticosterone (DOC)-treated rats. From the Clinica Medica (P.M., P.P.P., N.G.) and Farmacologia (M.V.V., M.P.D., M.C.F.), Sassari (Italy) University. Correspondence to Paolo Madeddu, MD, Clinica Medica, University of Sassari, Viale S. Pietro 8, 07100 Sassari, Italy. similar in rats given Ang II or vehicle. In deoxycorticosteronetreated rats total kallikrein was higher than in controls (9.2+0.8 versus 3.5±0.1 pkat/mg protein, P<.05), whereas active kallikrein did not differ (0.09±0.04 versus 0.09±0.03 pkat/mg protein, />=NS). A similar pattern was observed in uninephrectomized deoxycorticosterone-treated rats (active, 0.09±0.03 versus 0.10±0.04, P=NS; total, 7.4±0.7 versus 4.1 ±0.2 pkat/mg protein, F<.05). Kallikrein activity was higher in SHR compared with WKY rats (active, 0.34±0.04 versus 0.10±0.03; total, 9.5 + 1.2 versus 4.6±0.3 pkat/mg protein, P<.05). In conclusion, a kallikrein-like enzyme is present in rat aorta. The activity of this enzyme is elevated in rats with genetic hypertension, and it may be regulated by mineralocorticoids. (Hypertension. 1994;23[part 2]:899-902.)