Intravascular substance P dilates cerebral parenchymal vessels through a specific tachykinin NK1 receptor in cats.
The role of substance P in the cerebral parenchymal circulation was examined in 19 anesthetized cats. The local cerebral blood volume in the temporoparietal cortex was measured by our photoelectric method. Cerebral blood volume reflects the cumulative dimensions of the parenchymal microvessels. Intravenous injection of 0.01, 0.1, and 1 mg/kg FK888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl) carbonyl-L-prolyl]-N-methyl-N-phenylmethyl-3-(2-naphthyl)-L-alaninamide) , a selective tachykinin NK1 receptor antagonist, had no significant effects (compared to the vehicle, ethanol) on cerebral blood volume and mean arterial blood pressure. Intracarotid injection of 1, 10, 100 pmol/kg, and 1 nmol/kg substance P increased cerebral blood volume (P < 0.01) in a dose-dependent manner (maximal increase of 6.5% at 5 min). Following injection of 1 nmol/kg substance P, cerebral blood volume was initially reduced, possibly due to the marked fall in mean arterial blood pressure (P < 0.01). The cerebral blood volume increase elicited by 1 nmol/kg substance P was strongly blocked (P < 0.05) by prior injection of 1 mg/kg FK888. However, the depressor effect of 1 nmol/kg substance P (-24 +/- 4 mm Hg at 30 s, P < 0.01) was partially inhibited (P < 0.01) by FK888. We conclude that endogenous substance P may not have a significant role in the maintenance of resting tone of cerebral parenchymal vessels. Intravascular substance P, however, dilates the small microvessels through a specific tachykinin NK1 receptor and could be involved in the development of pathologic processes such as migraine headache.
Kobari
M
M
Department of Neurology, School of Medicine, Keio University, Tokyo, Japan.
Tomita
M
M
Tanahashi
N
N
Yokoyama
M
M
Takao
M
M
Fukuuchi
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001810:Blood Volume / Q000187:drug effects; D002339:Carotid Arteries; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000494:pharmacology; D007269:Injections, Intra-Arterial; D008833:Microcirculation / Q000187:drug effects; D018040:Receptors, Neurokinin-1 / Q000187:drug effects*; D013373:Substance P / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology*
D004151:Dipeptides; D007211:Indoles; D018040:Receptors, Neurokinin-1; D014665:Vasodilator Agents; C078949:FK 888; D013373:Substance P