Hypertensive dog plasma inhibits the Na+-K+ pump of cultured vascular smooth muscle.

Abstract

SUMMARY We investigated the effects of plasma from dogs with perinephritk hypertension on theReceived June 9, 1987; accepted March 24, 1988. cell for the putative humoral inhibitor in hypertension; intracellular ion concentrations are easily measured, facilitating data interpretation; and use of unprocessed plasma avoids creation, modification, release, or destruction of inhibitory or stimulatory factors by acidification, boiling, or freezing. 2 -3 There is evidence for humoral pump inhibitors in dogs with chronic one-kidney, one wrapped (1K1W) perinephritic hypertension.4 -5 However, the best evidence to date involves boiled plasma supernates assayed in rat tail artery strips. 3 In the present study, we used our homologous cultured cell assay to reexamine this form of hypertension. Fresh, unprocessed plasma obtained within 60 minutes of bleeding was layered over cultured dog aortic smooth muscle cells, and effects on 86 Rb + uptake were measured. To detect temporal changes in levels of humoral inhibitor, blood was assayed repeatedly over the first 6 weeks of hypertension. To detect endothelial cell modulation of the inhibition, we also assayed with cocultures. Finally, because there is evidence that humoral inhibitors in hypertensive rats may induce Na + -K + pump molecules in vascu-

Endothelial role in ouabain-induced contractions in guinea pig carotid arteries.

“…49 Inhibition of the vascular sodium pump by these compounds can be blocked by endotheliaJ cells. 39 In conclusion, one can speculate that the loss of a protective effect of the endothelium on sodium pump activity could facilitate vascular Na + ,K + -ATPase inhibition by endogenous circulating ouabainlike compounds. It is worth noting that the contractile effect of digitalis in human vessels is mainly due to direct actions of this agent on smooth muscle cells, 4 -50 -51 through which the possible antagonistic effects of the endothelium may have a greater physiological role.…”

“…39 This inhibition does not occur when those cells are cocultured with bovine endothelial cells. 39 Although those authors did not provide any explanation for their finding, it is consistent with our data. Also in agreement with our data, in guinea pig isolated trachea contractions induced by ouabain are potentiated by epithelium removal.…”