(Hypertension. 1997;29:510.)
© 1997 American Heart Association, Inc.
State-of-the-Art-Lecture |
Hypothalamic Substance P Release
Attenuated Angiotensin Responses in mRen2(27) Transgenic Rats
From the Hypertension Center, Bowman Gray School of Medicine at Wake Forest University, Winston-Salem, NC (D.I.D., B.F., S.M.B., B.M.W., J.K., C.M.F.), and the Max-Delbruck Center for Molecular Medicine, Berlin-Buch, Germany (D.G.).
Correspondence to Debra I. Diz, PhD, The Hypertension Center, Bowman Gray School of Medicine, Wake Forest University, Medical Center Blvd, Winston-Salem, NC 27157-1032. E-mail ddiz{at}bgsm.edu
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.
Key Words: angiotensin peptides • substance P • hypothalamus • renin transgenic rat • hypertension
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