Leucine aminopeptidase M significantly reduced blood pressure for up to 40 minutes when infused intracerebroventricularly into anesthetized spontaneously hypertensive rats (SHR) from a mean±SEM of 190±4 to 94±7 mm Hg and also in normotensive Wistar-Kyoto (WKY) rats from 138±5 to 68±8 mm Hg. Cerebrospinal fluid levels of angiotensin II (Ang II) and III were measured by radioimmunoassay and indicated drops with leucine aminopeptidase M infusion in SHR (from 36±6 to 11±1 pg/100 fil) and in WKY rats (from 33±9 to 13±1 pg/100 A»1). Pretreatment with the specific angiotensin receptor antagonist [Sar',Thr 8 ]Ang II (sarthran) significantly diminished the subsequent leucine aminopeptidase M-induced decreases in blood pressure in SHR and facilitated recovery to base level blood pressure and heart rate in both strains. Thus, exogenous application of leucine aminopeptidase M into the brain lateral ventricles of SHR is temporarily effective at reducing blood pressure, and this effect appears dependent on the brain angiotensinergic system. This treatment also reduced blood pressure in WKY rats; however, pretreatment with sarthran was reasonably ineffective at preventing subsequent leucine aminopeptidase M-induced decreases in blood pressure. (Hypertension 1989;13:910-915) S pontaneously hypertensive rats (SHR) and the stroke-prone SHR (SHRSP) appear to possess a dysfunctional brain reninangiotensin system that contributes to their hypertension.1 Schelling and colleagues 2 measured elevated levels of renin in brain areas associated with catecholaminergic nuclei in SHR, and Ganten et al 3 observed greater turnover of brain angiotensin than in normotensive rats. Our laboratory has measured deficiencies in brain aminopeptidase activity in SHR, 4 which may explain their heightened sensitivity to intracerebroventricularly injected angiotensin II (Ang II) 5 and angiotensin III (Ang III).
6Electrophysiological studies also indicate a significantly increased sensitivity to microiontophoretically injected Ang II and Ang HI in the paraventricular nucleus of SHR as compared with WistarKyoto (WKY) normotensive rats.
7From the