To study the effects of the selective neuropeptide Y (NPY) Y1 receptor antagonist BIBP 3226 in spontaneously hypertensive rats (SHR) in order to elucidate whether NPY function may be altered in the SHR and whether the NPY Y1 receptor plays a specific role in the maintenance of high blood pressure in this genetic form of hypertension.
Pithed and conscious SHR were studied after intravenous administration of 0.125–1 mg/kg BIBP 3226. The cardiovascular effects were evaluated under baseline conditions, under acute stress and after exogenous administration of 20 μg/kg NPY. The potentiating effects of NPY on pressor responses to phenylephrine and tyramine were studied in the SHR.
Intravenous administration of 0.125–1 mg/kg BIBP 3226 dose-dependently inhibited the pressor response to exogenous NPY in pithed SHR. At higher doses BIBP 3226 had an effect duration of 20–40 min. In the pithed SHR, a 0.5 mg/kg bolus injection of BIBP 3226 shifted the pressor response curve for exogenous NPY significantly to the right. It also inhibited significantly the potentiating effects of NPY on pressor responses to phenylephrine and tyramine. In conscious SHR, 0.125–1 mg/kg BIBP 3226 did not reduce the basal blood pressure. In combination with a hypotensive dose of prazosin, administration of 0.5 mg/kg BIBP 3226 had no added effects lowering the basal blood pressure. A stressful stimulus, namely an air jet, caused a brief increase in blood pressure and heart rate in the conscious SHR. In this model, 0.5 mg/kg BIBP inhibited the heart rate response slightly but had no effect on the blood pressure response.
Our results demonstrate that, although the selective NPY Y1 receptor antagonist BIBP 3226 may shift the pressor response to exogenous NPY potently, it does not influence basal blood pressure significantly in the SHR.