Alterations of renal vasopressin V1A and V2 receptors in spontaneously hypertensive rats.
To elucidate the role of arginine vasopressin (AVP) in a hypertensive state, the characteristics of renal cortex V(1A) and medulla V(2) receptors in young spontaneously hypertensive rats (SHR) during the developmental phase of hypertension were compared with those of age-matched Wistar-Kyoto (WKY) rats using the radioligand receptor assay technique. The systolic blood pressure of 8-week-old SHR was statistically significantly higher than that of WKY rats (142 +/- 1 vs. 125 +/- 2 mm Hg). The plasma AVP levels were also significantly higher in SHR than in WKY rats (3.20 +/- 0.41 vs. 1.96 +/- 0.34 pg/ml). In SHR, the maximum capacity of (3)H-d(CH(2))(5)Tyr(Me)AVP binding to cortical V(1A) receptors (B(max)) was statistically significantly higher than that of WKY rats (39.7 +/- 2.7 vs. 22.4 +/- 0.9 fmol/mg protein). Furthermore, the B(max) values of (3)H-AVP binding to medullary V(2) receptors in SHR were also significantly higher than in WKY rats (40.2 +/- 1.9 vs. 28.3 +/- 1.3 fmol/mg protein). However, the apparent dissociation constant (K(d)) values of renal cortex V(1A) and medulla V(2) receptors in SHR and WKY rats were not significantly different. These results indicate that increased amounts of renal cortex V(1A) and medulla V(2) receptors in SHR play an important role in the pathophysiology of hypertension.
Tahara
Atsuo
A
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical, Tsukuba, Japan. tahara@yamanouchi.co.jp
Tsukada
Junko
J
Tomura
Yuichi
Y
Wada
Koh-ichi
K
Kusayama
Toshiyuki
T
Ishii
Noe
N
Yatsu
Takeyuki
T
Uchida
Wataru
W
Taniguchi
Nobuaki
N
Tanaka
Akihiro
A
D000818:Animals; D001127:Arginine Vasopressin / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism*; D007679:Kidney Medulla / Q000378:metabolism*; D008297:Male; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017483:Receptors, Vasopressin / Q000378:metabolism*
D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin