Evidence for enhanced sodium transport in the tail artery of the spontaneously hypertensive rat.

Abstract

SUMMARY Transraembrane Na+ and K' gradients in the rat tail artery were dissipated by overnight incubation in K-free PSS at 10°C and then allowed to recover in normal physiologic salt solution (PSS) at 37°C. The active extrusion of Na + and uptake of K + during the recovery period was monitored with Na + and K + selective glass electrodes. Passive exchanges were differentiated by re-admitting K + at 3°C, or in the presence of 1 mM ouabain at both 3°C and 37°C. Active exchange was switched on by an abrupt transfer of the tissue from 3°C to 37°C. Active exchange, measured in perfused, supervised, or sequentially incubated arteries, was distinctly enhanced in young (16-, 20-and 26-week-old) spontaneously hypertensive rats (SHR) qf the Okamoto strain compared with age-matched Wistar-Kyoto normotensire (WKY) controls. No such difference was observed in rats with hypertension of 7 or 12 weeks' duration and equal severity induced by unilateral constriction of the renal artery. Steady-state Na, and K, were measured after washing the tissues for 45 minutes at 3°C in lithium-substituted medium to exchange extracellular sodium with lithium. Cell sodium in these tissues was further partitioned into a free component proportional to [Nab and an independent, constrained component. Cell potassium was found to be distinctly elevated in 2-and 4-month-old SHR, while free cell sodium remained normal, despite increased cell permeability demonstrable in a significant exchange of lithium for cell potassium and sodium even at 3°C. tence of increased ionic permeability and active transport activity in vascular smooth muscle in certain forms of experimental hypertension has steadily accumulaed. Beginning with Jones's observations 1 in the spontaneously hypertensive rat (SHR), isotope data obtained in his laboratory and ion-exchange data from ours have consistently implicated these factors in spontaneous and DOCAinduced hypertension.2 '' Both groups consider it likely that these altered membrane properties bear directly on the changes in contractile and biosynthetic functions of the vascular smooth muscle cell observed in these hypertensive states.The present report is concerned with a detailed quantitative kinetic examination of the relation between both sodium (Na + ) extrusion and potassium (K + ) uptake in the rat tail artery during recovery of the transmembrane ionic gradients following their dissipation by overnight incubation in cold K-free medium. These experiments were carried out with the standard Okamoto strain of SHR and its genetically related Wistar-Kyoto (WKY) normotensive controls. Parallel experiments in rats with renovascular hypertension are also reported. Observations concerning the steady-state transmembrane Na + and K + gradients in SHR and WKY animals are also described. MethodsMale albino rats of an inbred hypertensive strain and their matching controls, either obtained commercially (Charles River) or bred in this laboratory from NIH stock, were used for all experiments concerning 572 by guest on May 11, 2018 http...

Ouabain binding and Na+ content in resistance vessels and skeletal muscles of spontaneously hypertensive rats and K+-depleted rats.

“…Nevertheless, as regards the (Na); there does seem to be general agreement. After equilibration in physiological saline at physiological temperature, the (Na), in the aorta and tail artery of SHR and of age-matched normotensive controls is similar,' 4 which is in agreement with our findings in resistance vessels. As regards sodium fluxes, though, the situation is less clear.…”

Sodium pump activity in arteries of Dahl salt-sensitive rats.

“…These preincubation studies also provide evidence that cell energy stores in our freshly excised arterial tissues were not rate-limiting for pump activity, a possibility that has been suggested. 17 With regard to this relationship of intracellular sodium and pump activity, it is possible that the increases in pump activity we observed in tissues from the S rats reflected levels of [Na + ] t that were higher than those in control rats, even though identical methods of tissue excision and sodium-loading were used. This implies that levels of intracellular sodium in tissue from the control groups may have been sufficiently low to be rate-limiting for the pump.…”

“…17 Therefore, "Rb uptakes of freshly excised tail artery and aorta from 24 additional normotensive control rats (body weights 350 to 450 g) were measured after preincubating the tissues for 0, 60, 120, or 180 minutes in 37°C Krebs-Henseleit solution bubbled with O 2 -CO 2 , procedures that should return energy stores (and tissue ion contents) toward normal levels. We than sodium-loaded the tissues for 5 minutes and incubated them with M Rb, using methods identical to those described above.…”

<b>Purification and characterization of Na⁺,K⁺-ATPase from the kidney of spontaneously hypertensive and Wistar Kyoto </b><b>rats </b>

“…Alteration in the activity of Na+,K"-ATPase, a membrane enzyme primarily responsible for Na* and K* transport in most animal cells has been well investigated as one of the causes for changes in Na* and Ki distribution. In spontaneously hypertensive rats (SHR), an enhanced Na*,I(*-ATPase activity has been reported (7,8,10,22,28). On the other hand, other groups have reported similar (1) or reduced (12,13,18,25) levels of Na*,l(*-ATPase activity as compared with the normotensive control, Wistar Kyoto rats (WKY).…”