Sleep-disordered respiration in phenotypically normotensive, genetically hypertensive rats

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.