A co-morbidity of sleep apnoea is hypertension associated with elevated sympathetic nerve activity (SNA) which may result from conditioning to chronic intermittent hypoxia (CIH). Our hypothesis is that SNA depends on input to the rostral ventrolateral medulla (RVLM) from neurons in the paraventricular nucleus (PVN) that release arginine vasopressin (AVP) and specifically, that increased SNA evoked by CIH depends on this excitatory input. In two sets of neuroanatomical experiments, we determined if AVP neurons project from the PVN to the RVLM and if arginine vasopressin (V 1A ) receptor expression increases in the RVLM after CIH conditioning (8 h per day for 10 days). In the first set, cholera toxin β subunit (CT-β) was microinjected into the RVLM to retrogradely label the PVN neurons. Immunohistochemical staining demonstrated that 14.6% of CT-β-labelled PVN neurons were double-labelled with AVP. In the second set, sections of the medulla were immunolabelled for V 1A receptors, and the V 1A receptor-expressing cell count was significantly greater in the RVLM (P < 0.01) and in the neighbouring rostral ventral respiratory column (rVRC) from CIH-than from room air (RA)-conditioned rats. In a series of physiological experiments, we determined if blocking V 1A receptors in the medulla would normalize blood pressure in CIH-conditioned animals and attenuate its response to disinhibition of PVN. Blood pressure (BP), heart rate (HR), diaphragm (D EMG ) and genioglossus muscle (GG EMG ) activity were recorded in anaesthetized, ventilated and vagotomized rats. The PVN was disinhibited by microinjecting a GABA A receptor antagonist, bicuculline (BIC, 0.1 nmol), before and after blocking V 1A receptors within the RVLM and rVRC with SR49059 (0.2 nmol). In RA-conditioned rats, disinhibition of the PVN increased BP, HR, minute D EMG and GG EMG activity and these increases were attenuated after blocking V 1A receptors. In CIH-conditioned rats, a significantly greater dose of blocker (0.4 nmol) was required to blunt these physiological responses (P < 0.05). Further, this dose normalized the baseline BP. In summary, AVP released by a subset of PVN neurons modulates cardiorespiratory output via V 1A receptors in the RVLM and rVRC, and increased SNA in CIH-conditioned animals depends on up-regulation of V 1A receptors in the RVLM. Abbreviations Ang II, angiotensin II; AT1, angiotensin 1 receptor; AVP, arginine vasopressin; BIC, bicuculline; CIH, chronic intermittent hypoxia; CT-β, cholera toxin β subunit; D EMG , diaphragm electromyographic recording; ET-1, endothelin 1; FITC, fluorescein isothiocyanate; GG EMG , genioglossal electromyographic recording; HO-1, haem oxygenase 1; HPA, hypothalamic pituitary axis; HR, heart rate; IML, intermediolateral; L-NAME, N G -nitro-L-arginine methyl ester; MAP, mean arterial pressure; MDA, malondialdehyde; nNOS, neuronal nitric oxide synthase; NO, Sadly Musa A. Haxhiu died before this work was published.

Fibroblasts from EOM demonstrate distinct properties that distinguish them from leg muscle-derived fibroblasts. The distinct properties of EOM-Fibro may support the unique EOM phenotype and contribute to their differential involvement in disease.

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Conditioning with chronic intermittent hypoxia (CIH) causes hypertension associated with elevated sympathetic nerve activity and increased cardiorespiratory sensitivity to hypoxia. Hypoxia sensed by the carotid bodies drives cardiorespiratory regulating sites, including the PVN via the nucleus tractus solitarius. Our hypothesis is that CIH‐conditioning alters the balance of excitatory and inhibitory influences on CR control via the PVN. Male SD rats were exposed to CIH for 8 h/day for 10 days. Blood pressure (BP), heart rate (HR), diaphragm (DEMG) and genioglossus (GGEMG) activity were recorded in anesthetized, ventilated and vagotomized rats. The PVN was disinhibited by injecting bicuculline (BIC, a GABAA receptor antagonist, 100 pmol) before and after blocking AVP receptors in the RVLM with SR49059 (200 pmol/side, bilateral). In control rats, BIC increased BP, HR, minute DEMG and GGEMG. Following RVLM blockade, these variables were significantly decreased (p < 0.05). Although more pronounced, similar responses were observed in CIH‐conditioned rats; however, it required a higher dose of blocker (400 pmol/side, bilateral) to blunt the effect (p < 0.05). These finding suggests that AVP modulates cardiorespiratory output via the RVLM and CIH‐conditioned rats show augmented AVP transmission, suggesting AVP as a candidate neuropeptide that controls sympathetic tone and respiratory output during CIH.Supported by: HL 87620.

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