Increased blood pressure responses in neuropeptide Y transgenic rats

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology Vol. 281; no. 2; pp. 417 - R426
• Main Authors: Michalkiewicz, Mieczyslaw, Michalkiewicz, Teresa, Kreulen, David L, McDougall, Stuart J
• Format: Journal Article
• Language: English
• Published: United States 01.08.2001
• Subjects: Adrenergic alpha-Agonists - pharmacology; Animals; Animals, Genetically Modified; Blood Pressure - drug effects; Blood Pressure - physiology; Dose-Response Relationship, Drug; Female; Heart Rate - drug effects; Heart Rate - physiology; Hemorrhage - physiopathology; Male; Neuropeptide Y - genetics; Neuropeptide Y - metabolism; Norepinephrine - pharmacology; Rats; Rats, Sprague-Dawley; Time Factors; Vascular Resistance - physiology
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.2001.281.2.r417

1  Department of Physiology, West Virginia University, Morgantown, West Virginia 26506 - 9229; and 2  Michigan State University, Department of Physiology, B-340 Life Sciences, East Lansing, Michigan 48824 Considering the coexistence of neuropeptide Y (NPY) and norepinephrine in perivascular sympathetic nerves and the known vasoconstrictor cooperation of NPY with norepinephrine, we investigated the involvement of NPY in long-term control of cardiovascular functions using NPY transgenic (NPY-tg) rats. These rats were developed by injection of the rat (Sprague-Dawley) pronuclei with a 14.5-kb clone of the rat structural NPY gene. When compared with nontransgenic littermates, NPY concentrations were significantly increased in a number of cardiovascular tissues of NPY-tg hemizygotes. Direct basal mean arterial pressure and heart rate were not changed, but calculated total vascular resistance was significantly increased in NPY-tg subjects. Arterial pressure increases, in response to norepinephrine injection, were greater in the NPY-tg rats. Also, the hypotension and bradycardia in response to hemorrhage were significantly reduced in NPY-tg subjects. These results indicate that NPY, when expressed in increased amounts, potentiates the pressor effects of norepinephrine and contributes to maintaining blood pressure during hemorrhage, but it does not alter resting blood pressure. These transgenic rats will facilitate studies of the role of NPY signaling in cardiovascular regulation, particularly regarding its functional cooperation with norepinephrine. vasoconstriction; cardiac output; adrenoceptors; hemorrhage; hypersensitivity