Hypothalamic substance P release. Attenuated angiotensin responses in mRen2(27) transgenic rats.
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 degrees C with oxygenated Krebs' bicarbonate buffer. Substance P was measured before (basal) and during perfusion with either Krebs' buffer (control) or 2 mumol/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.
Diz
D I
DI
Hypertension Center, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, NC 27157-1032, USA. ddiz@bgsm.edu
Falgui
B
B
Bosch
S M
SM
Westwood
B M
BM
Kent
J
J
Ganten
D
D
Ferrario
C M
CM
D000803:Angiotensin I; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D030801:Animals, Genetically Modified; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D013373:Substance P / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D013373:Substance P; D000803:Angiotensin I; C118790:angiotensin I (1-7)