Hypothalamic Substance P Release

Abstract

Increases in arterial pressure and paraventricular nucleus vasopressin release in response to intracerebroventricular injections of angiotensin peptides are blunted in mRen2(27) renin transgenic [TG(+)] rats. Intraventricular injections of tachykinin peptides mimic several of the actions of angiotensin peptides, and angiotensin peptides evoke substance P release from hypothalamic brain slices. The present study assessed whether diminished substance P release occurs in response to angiotensin peptides in TG(+) rats. Systolic blood pressure at 8 to 12 weeks of age averaged 197±4 mm Hg (n=20; P <.05) in TG(+) rats compared with 123±4 mm Hg in normotensive control [TG(−)] rats (n=18). Body weight was lower in hypertensive than in normotensive rats (305±14 versus 344±13 g, respectively; P <.05). Brain slices from hypothalamus were perfused at 37°C with oxygenated Krebs’ bicarbonate buffer. Substance P was measured before (basal) and during perfusion with either Krebs’ buffer (control) or 2 μmol/L angiotensin-(1–7) or angiotensin II. Basal substance P release was 92±10 pg/g wet tissue in TG(+) and 98±12 pg/g in TG(−) rats ( P >.05). Angiotensin-(1–7) and angiotensin II significantly increased substance P release from hypothalamus of TG(−) rats (82% and 70% above control; P <.05) but not TG(+) rats. These studies further support the hypothesis that the cardiovascular effects of angiotensin peptides are mediated in part by substance P and that this relationship is blunted in a hypertensive model that results from excess tissue production of angiotensins.