1. The cardiovascular effects after intracerebroventricular injections of substance P were investigated in normotensive Wistar-Kyoto and in spontaneously hypertensive rats.
2. Substance P increased blood pressure in both rat strains. Wistar-Kyoto rats responded with moderate, dose-dependent blood pressure increases, and heart rate decreased; spontaneously hypertensive rats showed two- to three-fold increased pressor effects and, concomitantly, marked heart rate increases to intracerebroventricular injections of substance P.
3. Sino-aortic baroreceptor denervation rendered Wistar-Kyoto rats supersensitive to intracerebroventricular substance P to a similar degree as unoperated spontaneously hypertensive rats. Sino-aortic denervation had no effect on the blood pressure responses to the peptide in spontaneously hypertensive rats.
4. The central pressor actions of substance P could be markedly attenuated. by intracerebroventricular pretreatment with the derivative of γ-aminobutyric acid, baclofen.
5. We conclude that the baroreceptor reflex is disturbed in spontaneously hypertensive rats. Substance P may contribute to the pathogenesis of hypertension. The effector pathways appear to be different from angiotensin.