Substance P increases hypothalamic blood flow via an indirect adrenergic-cholinergic interaction.

1 Hypothalamic blood flow (HBF) was measured in conscious rabbits by the 133xenon washout technique. 2 Substance P in a dose of 50 or 500 ng increases HBF while 5 ng is without effect. 3 Cholinoceptor blockade, with either atropine or mecamylamine abolishes the vasodilator effect of substance P. 4 Chemical sympathectomy of the hypothalamus with 6-hydroxydopamine, or adrenoceptor blockade with either propranolol or phenoxybenzamine abolishes the effect of substance P on HBF. 5 Destruction of the intracerebral noradrenergic pathway (INP), or blockade of its vasodilator action, with barbiturate or bicarbonate, likewise prevent the vasodilator action of substance P. 6 These results suggest that substance P may cause an increase in HBF via the release of endogenous acetylcholine, which in turn stimulates the INP.