Patients with obstructive sleep apnea have an abnormal  peripheral vascular response to hypoxia

Remsburg, S; Launois, Sandrine; Weiss, J. Woodrow

doi:10.1152/jappl.1999.87.3.1148

Cited by 44 publications

(34 citation statements)

References 14 publications

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“…However others studies have reported enhanced AI in OSAS patients in the absence of increased peripheral pressure either shortly after awakening 20 or during the episode of apnoeas. 32 Increased sympathetic activity induced by hypoxia leads to paradoxical peripheral vasoconstriction, as previously shown by Resmurg et al 33 in OSAS patients exposed to isocapnic hypoxia. This may provoke increased amplitude of pressure waves from the level of the arterioles.…”

Section: Discussionmentioning

confidence: 78%

Structural and functional arterial properties in patients with obstructive sleep apnoea syndrome and cardiovascular comorbidities

Protogerou

Czernichow

et al. 2007

J Hum Hypertens

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The increased severity of obstructive sleep apnoea syndrome (OSAS) is associated with a parallel increase in the incidence of cardiovascular events. Whether the increased severity of OSAS is in fact associated with impaired arterial properties has never been thoroughly studied. In patients with OSAS who carry a high burden of cardiovascular risk factors, we investigated whether the severity of OSAS is associated with deterioration in the arterial properties, independent of classical cardiovascular risk factors. In 74 consecutive patients with OSAS, we non-invasively assessed, by means of tonometry and high-resolution ultrasound: carotid intima-media thickness (IMT), carotid diameter and plaques, carotid-femoral pulse wave velocity (PWV), central augmentation index (AI) and central blood pressures. The respiratory disturbance index was an independent predictor of IMT and PWV but not of carotid plaques, carotid diameter, AI or central blood pressures. Several parameters of nocturnal hypoxaemia were independently correlated with carotid IMT and PWV. In conclusion, arterial stiffening and thickening are modulated by the severity of OSAS, independently from age and cardiovascular risk factors.

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Section: Discussionmentioning

confidence: 78%

Structural and functional arterial properties in patients with obstructive sleep apnoea syndrome and cardiovascular comorbidities

Protogerou

Czernichow

et al. 2007

J Hum Hypertens

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“…Multiple pathways may therefore be implicated in potential abnormalities in efferent vasomotor control in response to hypoxia, and it is possible that several of these may be abnormal in type 2 diabetes. This is supported by findings that patients with obstructive sleep apnea and the metabolic syndrome, common comorbidities in type 2 diabetic subjects, exhibit abnormal sympathetic and paracrine control of vascular function (11,12), including abnormal vasomotor responses to hypoxia (11). To our knowledge, however, diabetic vascular responses to hypoxia have not previously been studied in humans, despite the fact that hypoxia is an important physiological stimulus associated with acute local and reflex vascular adaptations.…”

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confidence: 80%

Vasomotor Responses to Hypoxia in Type 2 Diabetes

et al. 2004

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Type 2 diabetes is associated with vascular dysfunction, accelerated atherosclerotic morbidity, and mortality. Abnormal vasomotor responses to chemoreflex activation may contribute to the acceleration of atherosclerotic diabetes complications, but these responses have not previously been investigated. We measured forearm mean blood flow (MBF) and mean vascular conductance (MVC) responses to isocapnic hypoxia in seven healthy and eight type 2 diabetic subjects during local intraarterial saline infusion and ␣-adrenergic blockade (phentolamine). The effects of hypoxia on saline and phentolamine responses significantly differed between groups; relative to normoxia, the %⌬MVC with hypoxia during saline was ؊3.3 ؎ 11.2% in control and 24.8 ؎ 13.3% in diabetic subjects, whereas phentolamine increased hypoxic %⌬MVC to similar levels (39.4 ؎ 9.7% in control subjects and 48.0 ؎ 11.8% in diabetic subjects, P < 0.05, two-way ANOVA). Absolute normoxic MBF responses during saline infusion were 91.9 ؎ 21.1 and 77.9 ؎ 15.3 in control and diabetic subjects, respectively, and phentolamine increased normoxic MBF to similar levels (165.2 ؎ 40.1 ml/min in control subjects and 175.9 ؎ 32.0 ml/min in diabetic subjects; both P < 0.05). These data indicate that diabetic and control subjects exhibit similar responses to hypoxia in the presence of ␣-adrenergic blockade despite evidence of exaggerated ␣-mediated vasoconstriction at rest. Diabetes 53: [2073][2074][2075][2076][2077][2078] 2004 T ype 2 diabetes is associated with accelerated atherosclerotic morbidity and mortality. It is characterized, early in its clinical course, by abnormal vascular function (1), which may ultimately contribute to the clinical manifestations of neuropathy and micro-and macrovascular disease. These abnormal vasomotor responses may be related to insulin resistance (2), hyperinsulinemia (3), hyperglycemia (4), endothelial dysfunction (1,5), dyslipidemia (3), or changes in sensitivity to norepinephrine (6). In particular, diabetes may be associated with abnormal sympathetic nervous system (SNS)-related vascular control. For example, several studies have demonstrated that hyperinsulinemia increases SNS activity (7,8) and that type 2 diabetic subjects exhibit increased peripheral norepinephrine-mediated ␣-adrenergic vasoconstriction for their level of SNS activity (6). Conversely, other studies (9) have demonstrated that patients with diabetes have decreased circulating plasma norepinephrine.Hypoxia is a common physiological stimulus that elicits chemoreflex-mediated changes in vasomotor control. In a recent study (10), we examined peripheral vasomotor response to hypoxia in healthy humans. Using the ␣-adrenergic receptor blocker phentolamine, we demonstrated that sympathetic vasoconstrictor tone masks underlying hypoxic vasodilatation, which was largely ␤-adrenoceptor mediated, possibly involving nitric oxide release. Multiple pathways may therefore be implicated in potential abnormalities in efferent vasomotor control in response to hypoxia, and it is possi...

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“…Increased sympathetic nervous system activity induced by the intermittent hypoxia that characteristically accompanies OSAS appears to mediate hypertension during OSAS via a mechanism that requires changes in the vasoreactivity of resistance vascular beds such as the kidney (13)(14)(15)(16)(17)(18)(19). Indeed, sustained hypoxia (SH) does not lead to hypertension as do pharmacologically-mediated decreases of angiotensin II levels and blockade of angiotensin receptors (20,21).…”

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confidence: 99%

Proteomic Analysis Reveals Alterations in the Renal Kallikrein Pathway during Hypoxia-Induced Hypertension

Thongboonkerd¹,

Gozal

Sachleben

et al. 2002

Journal of Biological Chemistry

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Obstructive sleep apnea syndrome (OSAS), a disorder characterized by episodic hypoxia (EH) during sleep, is associated with systemic hypertension. We used proteomic analysis to examine differences in rat kidney protein expression during EH, and their potential relationship to EH-induced hypertension. Young male Sprague-Dawley rats were exposed to either EH or sustained hypoxia (SH) for 14 (EH14/SH14) and 30 (EH30/SH30) days. Mean arterial blood pressure was significantly increased only in EH30 (p < 0.0002). Kidney proteins were resolved by two-dimensional-PAGE and were identified by MALDI-MS. Renal expression of kallistatin, a potent vasodilator, was down-regulated in all animals. Expression of ␣-1-antitrypsin, an inhibitor of kallikrein activation, was up-regulated in EH but down-regulated in SH. Western blotting showed significant elevation of B 2 -bradykinin receptor expression in all normotensive animals but remained unchanged in hypertensive animals. Proteins relevant to vascular hypertrophy, such as smooth muscle myosin and protein-disulfide isomerase were up-regulated in EH30 but were down-regulated in SH30. These data indicate that EH induces changes in renal protein expression consistent with impairment of vasodilation mediated by the kallikrein-kallistatin pathway and vascular hypertrophy. In contrast, SH-induced changes suggest the kallikrein-and bradykinin-mediated compensatory mechanisms for prevention of hypertension and vascular remodeling. To test the hypothesis suggested by the proteomic data, we measured the effect of EH on blood pressure in transgenic hKLK1 rats that overexpress human kallikrein. Transgenic hKLK1 animals were protected from EH-induced hypertension. We conclude that EH-induced hypertension may result, at least in part, from altered regulation of the renal kallikrein system.Obstructive sleep apnea syndrome (OSAS), 1 a disorder characterized by episodic hypoxia (EH), is a major public health problem (1-3). OSAS affects 4 -5% of the general adult population in United States and 1-2% of children (4 -6). One of the major consequences of untreated OSAS is systemic hypertension (7, 8), with a prevalence ranging from 15 to 56% (8 -10). Indeed, OSAS has been demonstrated to be an independent risk factor for systemic hypertension, and the relative risk is elevated even in young children (8, 11). Moreover, OSAS has also been associated with both proteinuria and end-stage renal disease (12).The pathophysiology of systemic hypertension in OSAS is complex. Increased sympathetic nervous system activity induced by the intermittent hypoxia that characteristically accompanies OSAS appears to mediate hypertension during OSAS via a mechanism that requires changes in the vasoreactivity of resistance vascular beds such as the kidney (13-19). Indeed, sustained hypoxia (SH) does not lead to hypertension as do pharmacologically-mediated decreases of angiotensin II levels and blockade of angiotensin receptors (20,21). These data suggest that changes in renal vasoconstrictors play a major role in the dev...

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Patients with obstructive sleep apnea have an abnormal peripheral vascular response to hypoxia

Cited by 44 publications

References 14 publications

Structural and functional arterial properties in patients with obstructive sleep apnoea syndrome and cardiovascular comorbidities

Structural and functional arterial properties in patients with obstructive sleep apnoea syndrome and cardiovascular comorbidities

Vasomotor Responses to Hypoxia in Type 2 Diabetes

Proteomic Analysis Reveals Alterations in the Renal Kallikrein Pathway during Hypoxia-Induced Hypertension

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