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 the following four 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); and 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 was higher in Control-1K, 1C than in Control-Sham rats (P < 0.05) and was higher in CIH-1K, 1C than in CIH-Sham rats (P < 0.05). However, the increase in mean arterial pressure in CIH-1K, 1C animals 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 hypotensive response in Con-1K, 1C compared with CIH-1K, 1C rats (P < 0.05), suggesting that sympathetic activity was attenuated in rats previously exposed to the 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.

Chronic intermittent hypoxia and renovascular hypertension: A case of one plus one equals one‐half!

“…Of note, previous work has shown no cumulative effect on the magnitude of hypertension of repeated exposures to chronic intermittent hypoxia separated by an equivalent recovery period of 15 days (Perim, Bonagamba, & Machado, ). Contrary to expectation, prior exposure to chronic intermittent hypoxia attenuated renovascular hypertension assessed in conscious rats after renal clipping (Perim et al., ). Moreover, the apparent ‘protective’ effect of preconditioning was absent in animals with selective carotid body ablation, preserving baroreflex function, which, surprisingly, was unaffected by the experimental stressors.…”

“…One wonders then what the outcome is for blood pressure regulation of a combination of exposure to chronic intermittent hypoxia and reduced renal artery flow. One variant of this question is addressed by Perim, Amorim, Bonagamba, and Machado () in this issue of Experimental Physiology .…”

“…As such, the study by Perim et al. () reveals occlusive effects of sequential pro‐hypertensive stimuli, revealing the capacity for persistent hypoxia‐dependent plasticity within the carotid body chemoreflex pathway that limits subsequent sympatho‐excitation in response to renal hypoperfusion. The precise mechanisms accounting for the arithmetic quandary producing an apparent hypo‐additive outcome remain unclear.…”

“…() that preconditioning has no discernible effect on renovascular hypertension after prior carotid body denervation, highlighting an obligatory role for carotid body afferent inputs to the central network. Moreover, because renovascular hypertension develops in carotid body‐denervated normoxic animals to a level equivalent to that of carotid body‐intact normoxic animals (Perim et al., ), it appears that one‐kidney, one‐clip hypertension in this setting does not depend upon potentiated chemoreflexes, as has been described in other models of renal hypertension (Pijacka et al., ). Yet, the suppression of renovascular hypertension by prior exposure to chronic intermittent hypoxia is carotid body‐dependent!…”

“…On the face of it, the finding of Perim et al. () is bewildering in the light of observations that chronic intermittent hypoxia causes epigenetic modifications affecting redox status within the nucleus tractus solitarii and efferent arm of the chemoreflex pathway, an effect requiring carotid body neural activity that underpins chronic intermittent hypoxia‐induced hypertension (Nanduri et al., ). The data of Perim et al.…”