Potassium inhibits cultured vascular smooth muscle cell proliferation

Increased dietary K+ increases plasma [K+] and is linked to or associated with reduced mortality from stroke and reduced blood pressure in humans and animals. We hypothesized that physiologic increases in extracellular [K+] ([K]o) directly inhibit cultured vascular smooth muscle cell (VSMC) proliferation. Studies were performed by stimulating quiescent cultured canine coronary artery and A7r5 VSMC with 5% serum at varying [K]o starting on day 0. When plated at 5,200 cells/cm2 A7r5 VSMC counts increased 121% by day 2 and 190% by day 6 in 3 mmol/L [K]o, but only 21% by day 2 and 45% by day 6 in 7 mmol/L [K]o; intermediate [K]o yielded intermediate proliferative rates. Serum caused a four- to fivefold increase in cell counts of cultured canine coronary artery VSMC in 7 days at 2 mmol/L [K]o of 2 mmol/L, and increasing [K]o to 7 mmol/L reduced proliferation by 68%. Uptake of [3H]thymidine by cultured canine coronary artery VSMC was inhibited by 50% between 2 and 7 mmol/L [K]o. Increased [K]o may act by decreasing intracellular Na+ ([Na]i). Exposure to serum for 24 h more than doubles canine coronary artery [Na]i, an effect previously associated with VSMC proliferation, and increased [K]o (from 2 to 7 mmol/L) reduces [Na]i by 74% before and 64% 24 h after serum. We conclude that physiologic increases in [K]o reduce [Na]i and proliferation of cultured VSMC. Similar effects occurring in vivo may help to account for the ability of increased dietary K+ to prevent vascular lesions.