Neurokinin1 receptor mediation of the vasodepressor effects of substance P in the nucleus of the tractus solitarius.
The involvement of substance P (SP) in cardiovascular regulatory mechanisms was investigated in the nucleus of the tractus solitarius (nTS) of urethane-anesthetized Wistar rats. Unilateral microinjections of SP (0.25 pmol in 50 nl) or the neurokinin (NK) 1 agonist [Sar9,Met(O2)11]-SP (0.25 pmol) resulted in decreases of blood pressure and heart rate when placed in the nTS but not in neighboring structures. Bilateral vagotomy abolished SP-induced bradycardia but did not prevent the vasodepression. Microinjection of the NK2 agonist alpha-NKA[4-10] (0.25 and 1.25 pmol) or the NK3 agonist senktide (0.25 and 1.25 pmol) had no effect on arterial pressure or heart rate. The relatively non-selective tachykininergic antagonist [D-Pro2,D-Trp7.9]-SP (10 pmol in 100 nl) and the NK1 antagonist cyclo(Gln-D-Trp-(N-Me)-Phe(R)Gly[ANC-2]Leu-Met)2 (1.25 pmol) prevented the cardiovascular effects of both SP and the NK1 agonist, whereas the NK2 antagonist cyclo(GlnTrpPheGlyLeuMet) was ineffective. Neither of the effective antagonists affected resting blood pressure, heart rate or the gain or threshold of the baroreflex. These data indicate that SP acts in the nTS via NK1 receptors to evoke a vagally-mediated bradycardia and a hypotension that is independent of changes of heart rate and suggest further that SP is not integral to the circuitry subserving the baroreflex.
Feldman
P D
PD
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans, USA.
D000595:Amino Acid Sequence; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D001919:Bradycardia / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D064729:Neurokinin-1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000378:metabolism; D013373:Substance P / Q000494:pharmacology*; D014628:Vagotomy
D064729:Neurokinin-1 Receptor Antagonists; D018040:Receptors, Neurokinin-1; D013373:Substance P