The effect of AVP-V2 receptor stimulation on local GFR in the rat kidney

Abstract

The effect of AVP-V2 receptor agonist desmopressin, dDAVP, its non-peptide antagonist OPC-31260 and vehicle infusion on glomerular filtration rate (GFR) in the outer, middle and inner cortex was studied in both hydropenic and water diuretic Inactin anaesthetized female Sprague-Dawley rats using the aprotinin method. Two subsequent GFR measurements were carried out in the same kidney by injection of 125I- and 131I-labelled aprotinin before and after i.v. infusion of dDAVP, OPC-31260 or the vehicle. Acute infusion of dDAVP in hydropenic rats increased total GFR by 14% relative to vehicle infusion, whereas in water diuretic rats it had no effect relative to vehicle. No significant changes in arterial pressure (Pa) or renal blood flow (RBF) were recorded. Infusion of OPC-31260 reduced total GFR by 11% compared with vehicle. These results are consistent with the findings that a presensitization of the vasculature by high plasma levels of AVP is necessary for the renal vascular effects mediated by the V2 or V2-like receptors to occur. The ratio between inner and outer cortex GFR remained unchanged from control to experimental condition as follows: dDAVP infusion in hydropenic rats, 0.504 vs. 0.494 in control; vehicle infusion in hydropenic rats, 0. 393 vs. 0.392; OPC-31260 infusion in hydropenic rats, 0.517 vs. 0. 523; dDAVP in water diuretic rats, 0.547 vs. 0.543; vehicle in water diuretic rats, 0.413 vs. 0.417. Thus no significant difference in the GFR response was observed between superficial and deep cortical layers of the rat kidney.

Vasopressin V2receptor expression along rat, mouse, and human renal epithelia with focus on TAL

“…In parallel with V 2 R expression, we found high-level baseline signals of phosphorylated NKCC2 in macula densa across species, suggesting that AVP may influence tubuloglomerular signaling via modulation of NKCC2-dependent transpepithelial transport. This observation may be related to AVP-dependent acute changes in glomerular filtration rate in rat kidney (4,37). However, the detection of selectively high phosphorylated NKCC2 immunoreactivity in DI rat macula densa underscores AVP-independent, constitutive activation of the cotransporter at this site.…”

“…These studies showed solid V 2 R expression in the CD, with some reference to regional differences in intensity believed to reflect AVPinduced effects on the stimulation/insertion of AQP-2 and urea transporter(s) (4,28,36). Localization of V 2 R was further reported in rat kidney TAL (10,39) and macula densa (32); binding of oxytocin, which is structurally related to AVP, and expression of oxytocin receptor in macula densa as well (33,45) support a role for AVP and, possibly, oxytocin in the regulation of glomerular filtration rate (37). A recent study analyzing V 2 R distribution in mouse and human kidney confirmed V 2 R expression in CD, but not in TAL (9).…”

Effects of Novel Vasopressin Receptor Antagonists on Renal Function and Cardiac Hypertrophy in Rats with Experimental Congestive Heart Failure

“…These effects are further supported by our findings that SR 49059 slightly improved GFR in CHF rats but not in sham controls rats 60 min after the drug administration. Moreover, by acting through V 1a , AVP causes contraction, proliferation, and hypertrophy of the mesangial cells, leading to decrease in GFR and ultrafiltration coefficient (Ganz et al, 1988;Roald et al, 2004). Taken together, the adverse renal and systemic effects of AVP mediated via V 1a may attenuate the diuretic action of SR 121463B in CHF by diverting the binding of the hormone selectively toward V 1a receptors.…”

Acutely elevated vasopressin increases circulating concentrations of cortisol and aldosterone in fasting northern elephant seal (Mirounga angustirostris) pups

“…VP has been implicated in the elevation of GFR in rats (Bouby et al, 1996;Roald et al, 2000), so we hypothesized that creatinine excretion would increase in response to acutely elevated [VP]. Although the net effect was no significant change in GFR following infusion of VP, the significant increase in plasma U:C ratio, a recognized indicator of altered filtration rate (Duarte and Preuss, 1993), suggests that filtration rate may have been acutely elevated as a consequence of the increase in [VP].…”

“…Aside from its role in tubular resorption of water, VP has also been implicated in elevating glomerular filtration rate (GFR) in rats (Bouby et al, 1996;Roald et al, 2000) and Na + excretion in dogs (Bie et al, 1984;Buckalew and Dimond, 1976;Chan and Sawyer, 1961;Johnson et al, 1979;Kompanowska-Jezierska et al, 1998;Smith et al, 1979;Sondeen and Claybaugh, 1989). Although infusion of hypertonic saline in fasting northern elephant seal pups induced a chronic (24·h) elevation in plasma [VP], GFR and Na + excretion, the contribution of elevated [VP] to an increase in GFR and Na + excretion could not be ascertained (Ortiz et al, 2002b).…”