Acute depressor actions of angiotensin II in the nucleus of the solitary tract are mediated by substance P.
Angiotensin II stimulates release of substance P from medulla oblongata slices, and low doses of substance P or angiotensin II injected into the nucleus of the solitary tract (NTS) decrease heart rate and mean arterial pressure. In this study, angiotensin II (250 fmol in 30 nl) was injected into the NTS of halothane-anesthetized male Sprague-Dawley rats before and after NTS injections of the substance P antagonist [Leu11, psi CH2NH-(10-11)]substance P (600 fmol in 60 nl). The substance P antagonist blocked the angiotensin II-induced hypotension and bradycardia (-16 +/- 3 mmHg and -24 +/- 7 beats/min before versus -0.3 +/- 1 mmHg and -2 +/- 3 beats/min after; P < 0.05). The depressor and bradycardic effects of glutamate were not altered by the substance P antagonist. In vitro receptor autoradiography showed that the substance P antagonist (10 or 100 microM) did not compete for 125I-labeled angiotensin II binding in the dorsal medulla, suggesting that the substance P antagonist does not interact directly with angiotensin II receptors. We conclude that the cardiovascular effects of angiotensin II in the NTS are mediated at least in part by substance P.
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Hypertension Center, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157-1032, USA.
Fantz
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Benter
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Bosch
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D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure / Q000187:drug effects*; D018698:Glutamic Acid / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000032:analysis / Q000378:metabolism*; D017552:Solitary Nucleus / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D007457:Iodine Radioisotopes; D011945:Receptors, Angiotensin; C107563:substance P, Leu(11),CH2NH-(10-11)-; D000804:Angiotensin II; D013373:Substance P; D018698:Glutamic Acid