Alterations of Renal Vasopressin V_1A and V₂ Receptors in Spontaneously Hypertensive Rats

Abstract

To elucidate the role of arginine vasopressin (AVP) in a hypertensive state, the characteristics of renal cortex V_1A and medulla V₂ 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 ³H-d(CH₂)₅Tyr(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 ³H-AVP binding to medullary V₂ 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 V₂ receptors in SHR and WKY rats were not significantly different. These results indicate that increased amounts of renal cortex V_1A and medulla V₂ receptors in SHR play an important role in the pathophysiology of hypertension.

Increased expression of ENaC subunits and increased apical targeting of AQP2 in the kidneys of spontaneously hypertensive rats

“…On the other hand, the change of ␣-ENaC was relatively minimal, with only a mild increase in the ISOM in 6-wk SHR. The changes in expression fit the previously described patterns seen in response to vasopressin treatment (17); because vasopressin levels and its responsiveness have been shown to be increased in SHR (13,27,42,53), the observed changes in expression are consistent with this view. Increased sodium reabsorption in the collecting duct is correlated with the increased protein abundance of ENaC subunits at the site of function, i.e., in the plasma membrane.…”

“…The excessive retention of sodium in SHR may result from either a reduced glomerular filtration rate (GFR) (15,53) or an enhanced tubular reabsorption (40) or both. The activities of Na-K-ATPase and sodium/ hydrogen exchanger in the proximal tubule was found to be significantly higher in young SHR compared with age-matched Wistar-Kyoto rats (WKY) (21,40), and these changes may account in part for the increased ECF volume expansion in SHR.…”

Increased Expression of Renal Aquaporin Water Channels in Spontaneously Hypertensive Rats

“…The importance of AVP and V 2 receptor signaling in the development of hypertension has been supported in SHR [10,11] . Indeed, the urine was more concentrated with its volume decreased in SHR in the present study.…”

“…The importance of AVP and V 2 receptor signaling in the development of hypertension has been also supported in spontaneously hypertensive rats (SHR) [10,11] . In addition, the urinary excretion and the renal expression of AQP2 are increased in SHR [5,7] .…”

Enhanced Ca2+response to AVP in preglomerular vessels from rats with genetic hypertension during different hydration states

“…We have previously shown that preglomerular arterioles of 8-wk-old SHR express approximately two-to three-times as many V 1a receptors normalized to milligram tissue protein as do vessels of age-matched WKY under euvolemic conditions (50), an observation recently confirmed (41). PCR analysis reveals that the reason for the elevated receptor number likely results due to twice the amount of V 1a mRNA (50).…”