Sleep-disordered Respiration in Phenotypically Normotensive, Genetically Hypertensive Rats

Abstract

Increased prevalence of sleep-related breathing disorders has been reported in patients with essential hypertension and we have described disordered breathing in spontaneously hypertensive rats, an animal model of genetic hypertension. The mechanisms coupling hypertension to respiratory dysfunction during sleep remain, however, largely unknown. To determine if sleep-related respiratory disorder reflects cardiovascular derangement or, alternatively, represents an independent phenotype in hypertensive rats, we polygraphically recorded groups (n = 10) of genetically hypertensive, genetically normotensive, and phenotypically normotensive rats carrying a genetic background for hypertension. Apnea index was elevated more than 15-fold during NREM sleep in both animal groups carrying hypertension-related genes (p < 0.0001 for each) versus normotensive Wistar Kyoto rats. During REM sleep, a genetic background for hypertension was associated with an increased apnea index of at least 500% versus normotensive Wistar Kyoto rats (p < 0.0001 for each comparison). Still, overall mean respiratory rate, minute ventilation, and sleep architecture were equivalent among all animal groups. As expected, blood pressure and heart period were similar in both normotensive groups but elevated in the hypertensive animals. Persistent sleep-related breathing disorder despite effective cardiovascular normalization in the phenotypically normotensive but genetically hypertensive rats suggests that disordered breathing represents a genetically determined phenotype in these animals that is not secondary to the cardiovascular derangements. The model system described here may provide a powerful tool for investigation of the determinants of sleep-related breathing disorder.

Effects of orexin 2 receptor activation on apnea in the C57BL/6J mouse

“…Reductions in spontaneous sleep apnea (>2 respiratory cycles) occurred using either pharmacologic agent. The latter study concluded that a persistent sleep-related breathing disorder occurred despite effective cardiovascular normalization by neonatal hydralazine in the phenotypically normotensive but genetically hypertensive rat (Carley et al, 2000). In the former study mirtazapine was observed to suppress apnea >2 respiratory cycles in all sleep stages in adult rats and attributed this effect to a mixed agonist/antagonist profile at serotonin receptors (Carley and Radulovacki, 1999).…”

Effects of long-term captopril andl-arginine treatment on ventilation and blood pressure in obese male SHHF rats

“…Thus NO production in peripheral chemoreceptors or the central nervous system alone did not solely contribute to the results reported in this study; rather, a remodeling of central regulation of frequency may have occurred. Cap treatment, however, did not prevent the development of periodic breathing, a finding also described in SHR (4). Additional mechanisms by which Cap may maintain ventilation is altering reflex responses to elevated blood pressure (10).…”

The efficacy of antihypertensive drugs in chronic intermittent hypoxia conditions

“…The natural models of sleep apnea include the English bulldog, the historic natural model of spontaneous obstruction (Hendricks et al, 1987), the sleep-related central apnea models [e.g., Sprague-Dawley rats (Carley et al, 2000), spontaneously hypertensive (SH) rats (Carley et al, 1998), C57BL/6J (Julien et al, 2003; Liu et al, 2010)], and the Zucker obese rat in which apnea is obesity-related (Ray et al, 2007; Lee et al, 2008; Iwasaki et al, 2012). The experimentally-induced models (e.g., the sleep deprivation model, induced airway obstruction and the CIH model) are the most widely used.…”