Vasopressin V1A receptor enhances baroreflex via the central component of the reflex arc.
The neurohypophyseal peptide [Arg(8)]-vasopressin (AVP) exerts its physiological actions via 3 distinct receptor isoforms designated V1A, V1B, and V2. We recently showed that V1A receptor was involved in the baroreflex control of heart rate using V1A receptor knockout mice. The present study was undertaken to further clarify this finding. In conscious mice, resting blood pressure of the knockout group was lower than that of the wild-type group (wild-type, 108+/-2.0 mm Hg; knockout, 98+/-3.8 mm Hg; n=6-7) without notable change in heart rate. Although phenylephrine and nitroprusside-induced changes in blood pressure did not differ in these strains, the subsequent bradycardia and tachycardia were markedly blunted in the knockout mice (mean slopes for baroreflex curve after phenylephrine treatment; wild-type, -5.65+/-0.30 bpm/mm Hg; knockout, -3.97+/-0.52 bpm/mm Hg; those after nitroprusside treatment; wild-type, -0.51+/-0.10 bpm/mm Hg; knockout, -0.18+/-0.05 bpm/mm Hg; n=6-7). Under urethane anesthesia (1.0-1.2 g/kg, i.p.), electrical stimulation of the vagal afferent nerve evoked frequency-dependent hypotension and bradycardia in the wild-type mice. In contrast, in the knockout mice such stimulation induced a pressor, not a depressor, response and diminished bradycardia. Moreover, electrical stimulation-induced hemodynamic changes through the vagal afferent nerve in the wild-type mice were significantly attenuated by pretreatment with intravenously administered V1A receptor antagonist d(CH(2))(5)Tyr(Me)AVP. Electrical stimulation of the vagal efferent nerve-induced hemodynamic changes (depressor and bradycardia) and chronotropic responses to adrenergic and cholinergic stimuli were not different between the 2 strains. These results suggest that the V1A receptor in the central nervous system is involved in the regulation of the heart rate via the baroreflex arc.
Oikawa
Ryo
R
Department of Molecular and Cellular Pharmacology, Tokyo University of Pharmacy and Life Science, 1432-1, Horinouchi, Hachioji, Tokyo, Japan.
Nasa
Yoshihisa
Y
Ishii
Rie
R
Kuwaki
Tomoyuki
T
Tanoue
Akito
A
Tsujimoto
Gozoh
G
Takeo
Satoshi
S
D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D001794:Blood Pressure; D001921:Brain / Q000502:physiology*; D004558:Electric Stimulation; D006339:Heart Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017483:Receptors, Vasopressin / Q000502:physiology*; D014630:Vagus Nerve / Q000502:physiology
D017483:Receptors, Vasopressin