Regulation of intracellular pH in the spontaneously hypertensive rat. Role of bicarbonate-dependent transporters.

Abstract

Previous studies that have evaluated the Na + -H + antiporter in cells from hypertensive subjects were generally performed under conditions in which HCO 3 -CO 2 , the physiological buffer system, was absent from the assay media. The objective of this study was to evaluate the activity of the Na + -H + antiporter and that of the Na + -dependent and Na + -independent Cr-HCO 3 " exchangers in cells assayed in the presence of HCO3-CO2 in the media. Lymphocytes from 6-to 8-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) rats were obtained from the thymus gland and assayed immediately after isolation. The activity of the Na + -H + antiporter after stimulation by cell acidification (pH, approximately 6.4) was similar in SHR and WKY rats (18.67+1.03 and 16.12±0.92 mmol H + /L per minute, respectively). Recovery from cell alkalinization was effected by an Na + -independent C1~-HCO 3~ exchanger, with maximal activity at an alkaline pH, (approximately 7.7). The stimulated activity of this Na + -independent Cr-HCO 3 " exchanger was also not different between SHR and WKY cells (2.65±0.25 and 2.55±0.32 mmol H + /Lper minute, respectively). Acute chloride removal produced a rise in pH, that was Na + -dependent and sensitive to 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS) but resistant to ethylisopropylamiloride (EIPA), reflecting the activity of an Na + -dependent C1~-HCO 3~ ex-O ver the last several years the investigation of intracellular proton concentration and the Na + -H + antiporter in experimental 16 and clinical 7 " 14 hypertension has received increasing attention. Previous studies that have evaluated the Na + -H + antiporter in cells from hypertensive subjects were performed under conditions in which bicarbonate-carbon dioxide (HCO 3 -CO 2 ), the physiological buffer system, was absent from the assay media. This, by design, results in an overestimation of the role of the Na + -H + antiporter in the regulation of intracellular pH (pH|) and ignores the existence of other HCO 3~-dependent transporters that contribute not only to the regulation of pH| 15 -17 but also to the regulation of cell volume, 1819 cell growth, 2021 and intracellular sodium. 22 Alterations in the control of any or all of these processes could in various ways be involved in the pathogenesis of hypertension. 2 - 3910 -23 Received September 10, 1993; accepted in revised form December 21, 1993.From Northwestern University Medical School and Lakeside Veterans Administration Hospital, Chicago, Illinois.Correspondence to Daniel Batlle, MD, Division of Nephrology and Hypertension, Northwestern University Medical School, 310 E Superior, Morton Bldg 3-615, Chicago, IL 60611.changer. Unlike the Na + -H + exchanger and the Na + -independent C1"-HCO 3 " exchanger, which had their highest activities at extremes of pH, (low pH|, Na + -H + exchanger, and high pH, Na + -independent C1"-HCO 3 " exchanger), the Na + -dependent G~-HCO 3~ exchanger had its maximal activity near steady-state pH, (approximately...

Abnormalities of membrane function and lipid metabolism in hypertension A review

“…195 Alterations of intracellular pH regulation are also present in hypertensive animals. Decreased pH i was found in lymphocytes of SHR, 196,197 Mü nster hypertensive rats, 198 and Dahl salt-sensitive rats, 171 as well as in erythrocytes of rats with experimental hypertension. 174 Moreover, lower pH i was seen in platelets of salt-sensitive Sabra and Dahl rats 199,200 but not in those of rats with spontaneous hypertension.…”

“…Nevertheless, it should be noted that pH i in resistance arteries of SHR was increased only in young, 5-week-old, but not in adult, 12-week-old, animals 203 ; increased pH i in resistance arteries of adult SHR was only observed in absence of bicarbonate 205 ; and higher pH i seen initially in cultured VSMC from SHR disappeared after several passages. 204 In contrast to the scarce information about the activity of HCO 3 Ϫ /Cl Ϫ exchangers in genetic hypertension, 197,208 Na ϩ /H ϩ exchanger activity is increased in various blood cells 179,209,210 and cultured VSMC of SHR. 202,207,211 The enhanced rate of Na ϩ /H ϩ exchange in SHR is ascribed to increased V max , whereas further kinetic alterations of the Na ϩ /H ϩ exchanger are still uncertain.…”

Intracellular acidification associated with changes in free cytosolic calcium. Evidence for Ca2+/H+ exchange via a plasma membrane Ca(2+)-ATPase in vascular smooth muscle cells.

“…Readdition of chloride resulted in a prompt restoration of pHi to baseline (Fig. 8), an effect which is thought to be due to operation of the Na-independent Cl/HCO3 exchanger (33,34). In the presence of 50 MM DIDS, the pH, fall on readdition of chloride was completely blocked (Fig.…”

“…1, occur with a wide array of vasoactive compounds and growth factors. pHi regulation is generally accomplished via well known plasma membrane transporters (Na/H exchange, Na-dependent Cl/HCO3 exchange, and Na-independent Cl/HCO3 exchange) which, acting in concert, prevent departures of pHi from normal (6,7,33,34 Figs. 1 and 4).…”

Characterization of the Na+/HCO3-Cotransport in Human Neutrophils

“…Surprisingly, information on the presence of bicarbonate transporters in neutrophils is scarce. The Na + /HCO 3 - cotransport (NBC) has crucial roles in regulating pH i in a variety of cells, including cardiac, vascular smooth-muscle, glial and renal cells [2,3,4,5], and blood cells as lymphocytes [6], monocytes [7] and platelets [8]. However, the presence of NBC in neutrophils has not been reported yet.…”