Increased blood pressure responses in neuropeptide Y transgenic rats

Considering the coexistence of neuropeptide Y (NPY) and norepinephrine in p erivascular sympathetic nerves and the known vasoconstrictor cooperation of NPY with norepinephrine, we investigated the involvement of NPY in long-te rm control of cardiovascular functions using NPY transgenic (NPY-tg) rats. These rats were developed by injection of the rat (Sprague-Dawley) pronucle i with a 14.5-kb clone of the rat structural NPY gene. When compared with n ontransgenic littermates, NPY concentrations were significantly increased i n a number of cardiovascular tissues of NPY-tg hemizygotes. Direct basal me an arterial pressure and heart rate were not changed, but calculated total vascular resistance was significantly increased in NPY-tg subjects. Arteria l pressure increases, in response to norepinephrine injection, were greater in the NPY-tg rats. Also, the hypotension and bradycardia in response to h emorrhage were significantly reduced in NPY-tg subjects. These results indi cate that NPY, when expressed in increased amounts, potentiates the pressor effects of norepinephrine and contributes to maintaining blood pressure du ring hemorrhage, but it does not alter resting blood pressure. These transg enic rats will facilitate studies of the role of NPY signaling in cardiovas cular regulation, particularly regarding its functional cooperation with no repinephrine.