Abstract-Chronic intermittent hypoxia, a characteristic feature of sleep-disordered breathing, induces hypertension through augmented sympathetic nerve activity and requires the presence of functional carotid body arterial chemoreceptors. In contrast, chronic sustained hypoxia does not alter blood pressure. We therefore analyzed the biosynthetic pathways of catecholamines in peripheral nervous system structures involved in the pathogenesis of intermittent hypoxia-induced hypertension, namely, carotid bodies, superior cervical ganglia, and adrenal glands. Rats were exposed to either intermittent hypoxia (90 seconds of room air alternating with 90 seconds of 10% O 2 ) or to sustained hypoxia (10% O 2 ) for 1 to 30 days. Dopamine, norepinephrine, epinephrine, dihydroxyphenylacetic acid, and 5-hydroxytyptamine contents were measured by high-performance liquid chromatography. Expression of tyrosine hydroxylase and its phosphorylated forms, dopamine ␤-hydroxylase, phenylethanolamine N-methyltransferase, and GTP cyclohydrolase-1 were determined by Western blot analyses. Both sustained and intermittent hypoxia significantly increased dopamine and norepinephrine content in carotid bodies but not in sympathetic ganglia or adrenal glands. In carotid bodies, both types of hypoxia augmented total levels of tyrosine hydroxylase protein and its phosphorylation on serines 19, 31, 40, as well as levels of GTP cyclohydrolase-1. However, the effects of intermittent hypoxia on catecholaminergic pathways were significantly smaller and delayed than those induced by sustained hypoxia. Thus, attenuated induction of catecholaminergic phenotype by intermittent hypoxia in carotid body may play a role in development of hypertension associated with sleep-disordered breathing. The effects of both types of hypoxia on expression of catecholaminergic enzymes in superior cervical neurons and adrenal glands were transient and small. Key Words: blood pressure Ⅲ catecholamines Ⅲ chemoreceptors Ⅲ sympathetic nervous system Ⅲ sleep apnea syndromes Ⅲ oxygen Ⅲ adrenal gland S leep-disordered breathing (SDB) is a frequent condition that affects Ϸ5% of the population and is characterized by repetitive episodes of hypoxemia and hypercapnia, followed by arousal, respiratory recovery, and reoxygenation. Persistent SDB is causally associated with substantial cardiovascular morbidity, the most important being systemic arterial hypertension (for recent comprehensive review, see Fletcher, 2003 1 ). The mechanisms involved in the genesis of this hypertension appear to involve several different components including augmented sympathetic nerve activity, 1-4 altered function of arterial chemoreceptors, 1,5-7 elevated levels of circulating norepinephrine (NE), 8 -10 decreased vascular responses to nitric oxide, 11 increased plasma concentrations of endothelin, 12,13 and altered regulation of the renal kallikrein-kallistatin pathway. 14 The use of animal model systems in which different components of SDB can be studied individually have revealed that intermittent hy...

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Blood flow is essential for normal bone growth and bone repair. Like other organs, the regulation of blood flow to bone is complex and involves numerous physiologic mechanisms including the sympathetic nervous system, circulating hormones, and local metabolic factors. Our studies addressed the following questions: (1) Which endogenous vasoconstrictor agents regulate in vivo blood flow to bone? (2) Does a decrease in bone vascular reactivity to vasoconstrictor hormones account for the increase in blood flow during bone healing? (3) Does the endothelium influence bone arteriolar function? An intact bone model was developed in the rat to assess hormonal regulation of in vivo bone blood flow and in vivo bone vascular reactivity. An isolated, perfused bone arteriole preparation was employed to characterize the responsiveness of small resistance-size arterioles (diameter < 100 µm) to vasoconstrictor hormones and to evaluate the role of the vascular endothelium to modulate vascular smooth muscle reactivity. Our results indicate that: (1) though exogenous endothelin is a potent constrictor of the in vivo bone vasculature, endogenous endothelin does not actively regulate in vivo blood flow; (2) the increase in blood flow to a bone injury site is not due to a decrease in bone vascular sensitivity to norepinephrine, and (3) isolated bone arterioles of young rats are very sensitive to vasoconstrictor hormones but exhibit only modest endothelium-mediated vasodilation.

causes hypotension by activating pulmonary sympathetic afferents in the rabbit. J Appl Physiol 95: 233-240, 2003. First published April 4, 2003 10.1152/japplphysiol.00584.2002 activates sympathetic afferents in the heart, intestine, and kidney, and it alters hemodynamics. However, we know little about the influence of pulmonary sympathetic afferents on circulation. Activation of pulmonary afferents by directly injecting stimulants into the lung parenchyma permits examination of reflexes that originate in the lung without confounding effects from the systemic circulation. In the present study, we tested the hypothesis that pulmonary sympathetic afferents exert a significant influence on hemodynamics. We examined reflex effects of injecting BK (1 g/kg in 0.1 ml) into the lung parenchyma on circulation in anesthetized, open-chest, artificially ventilated rabbits. BK significantly decreased mean arterial blood pressure (BP) (27 Ϯ 3 mmHg) and heart rate (19 Ϯ 4 beats/min). Both effects remained after bilateral vagotomy. To rule out possible direct systemic vasodilation by BK, we examined renal sympathetic nerve activity (RSNA) in response to BK injection and examined BP responses to injection of ACh (0.1 ml of 10 Ϫ4 M). BK suppressed the RSNA before and after vagotomy. ACh did not change BP when injected into the lung parenchyma, but it decreased BP (31 Ϯ 3 mmHg) when injected into the right atrium. Our data indicate that activating pulmonary sympathetic afferents reflexly suppresses hemodynamics. lung receptors; lung reflex; depressor effect; bradycardia FOR DECADES IT HAS BEEN RECOGNIZED that cardiovascular regulation is strongly influenced by inputs from the lung (24). These pulmonary inputs are believed to travel mainly in the vagus nerves. Mechanically activating pulmonary stretch receptors (33) or chemically activating pulmonary C fibers (4) in the vagus nerve can cause peripheral vasodilation and changes in heart rate. Activation of some pulmonary vagal afferents in the rabbit causes a slight pressor response in addition to stimulating breathing (25, 34). However, information regarding the reflex effects evoked from pulmonary sympathetic afferents is scarce and debatable (23).Sensory information in the lung is transmitted through vagal and sympathetic nerves (32). Morphological evidence points to the existence of sympathetic afferents in the lungs (13,18,22). Pulmonary sympathetic afferent activity has been recorded in stellate ganglia (9) and white rami of T 2