Regulation of luminal alkalinization and acidification in the cortical collecting duct by angiotensin II

Abstract

Angiotensin II (ANG II) regulates whole kidney ion transport, yet its effects in the collecting duct are unknown. The purpose of these studies was to determine whether ANG II regulates luminal alkalinization and acidification in the rabbit cortical collecting duct (CCD). The rate of luminal alkalinization or acidification was measured as the rate of change of luminal fluid pH under stop-flow conditions using in vitro microperfused CCD segments. Outer CCD alkalinized the luminal fluid, consistent with net HCO3- secretion. Addition of ANG II, 10(-7) M, to the peritubular solution for 30 min significantly stimulated luminal alkalinization. The stimulatory effect of ANG II was not due to time-dependent effects and was blocked by peritubular addition of the ANG II type 1 (AT1) receptor antagonist, losartan, at 10(-6) M. Losartan, 10(-6) M, when added to the peritubular solution, did not alter the rate of luminal alkalinization independent of ANG II. In contrast, peritubular ANG II, 10(-7) M, did not alter inner CCD luminal acidification. Addition of ANG II to the peritubular solution at the lower concentration of 10(-10) M did not alter the rates of luminal alkalinization and acidification in the outer and inner CCD, respectively. Peritubular ANG II, 10(-7) M, but not vehicle, stimulated B cell apical HCO3- secretion occurring in response to peritubular Cl- removal. These studies demonstrate that ANG II acts through a basolateral AT1 receptor to stimulate outer CCD luminal alkalinization via, at least in part, B cell stimulation.

The Intrarenal Renin-Angiotensin System: From Physiology to the Pathobiology of Hypertension and Kidney Disease

“…Despite a dramatic up-regulation of H ϩ secretion in the proximal and distal tubules by Ang II, infusion of Ang II does not produce a metabolic alkalosis, suggesting a compensatory regulation of acid secretion in other segments of the nephron. To support this notion, Ang II decreased H ϩ secretion in the perfused rat outer medullary collecting ducts (Weiner et al, 1995;Wall et al, 2003). This can be explained by a reduction in H ϩ -ATPase activity (Tojo et al, 1994;Valles and Manucha, 2000).…”

Renal Vacuolar H+-ATPase

“…In all cases where the pharmacological profile was determined, stimulation occurred through AT 1 receptors (233). In contrast, one study reported a reduction in cortical collecting duct vacuolar H ϩ -ATPase enzymatic activity in response to angiotensin II (510), another an increase of bicarbonate secretion in isolated rabbit cortical collecting duct (559). In addition, in perfused rat outer medullary collecting duct, a reduction in bicarbonate reabsorption after application of angiotensin II was found (549).…”

ANG II, ANG-(1-7), ALDO and AVP biphasic effects on Na+/H+ transport: the role of cellular calcium

“…While the biphasic effects of ANG II on proximal tubular transport have been studied in rats, mice, and rabbits [101][102][103][104][105], little is known about the effects of ANG II on human proximal transport. However, recently, Shirai and colleagues found that in human cells, ANG II, unlike what was observed in other species, induced the dose-dependent and strong stimulation of human proximal tubular transport via the activation of AT1-dependent nitric oxide/guanosine 3', 5'-cyclic monophosphate/ERK [106].…”

“…In the rabbit cortical collecting duct, peritubular ANG II stimulated β cell apical HCO 3-secretion through a basolateral AT1 receptor [105]. In intercalated cells of connecting tubules and cortical collecting ducts, ANG II stimulated H + -ATPase and may have contributed to the regulation of chloride reabsorption and bicarbonate secretion [110].…”