Previous exposure to chronic intermittent hypoxia blunts the development of one-kidney one-clip hypertension in rats

Abstract

Chronic intermittent hypoxia (CIH) and one-kidney one-clip (1K, 1C) experimental models lead to sympathetic overactivity and hypertension. We hypothesized that previous exposure to CIH potentiates the development of 1K, 1C renal hypertension. Male rats were divided into 4 groups: Control-1K, 1C, maintained under normoxia followed by 1K, 1C surgery (n = 19); Control-Sham, maintained under normoxia, followed by Sham surgery (n = 19); CIH-1K, 1C, exposed to CIH (10 days) and 1K, 1C surgery (n = 19); CIH-Sham, exposed to CIH and Sham surgery (n = 18). Animals were catheterized 8 days after 1K, 1C or Sham surgeries and cardiovascular and respiratory parameters recorded on the following day. Baseline mean arterial pressure (MAP) was higher in Control-1K, 1C than in Control-Sham rats (P < 0.05), as well as higher in CIH-1K, 1C than in CIH-Sham rats (P < 0.05). However, the increase in MAP in CIH-1K, 1C was significantly blunted in comparison to Con-1K-1C rats (P < 0.05) indicating that previous exposure to CIH attenuates the development of renal hypertension. Systemic administration of hexamethonium, a ganglionic blocker, promoted a larger hypotension response in Con-1K-1C compared to CIH-1K-1C rats (P < 0.05), suggesting that sympathetic activity was attenuated in rats previously exposed to CIH protocol. In addition, removal of the carotid bodies before 1K, 1C renal hypertension eliminated the protective effect of CIH preconditioning on the development of the 1K, 1C hypertension. We conclude that previous exposure to CIH attenuates the development of renal hypertension via a carotid body-dependent mechanism.

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