Pathogenesis Of Hypertension In Patients Research Articles

Динаміка маркерів запалення у пацієнтів з легеневою гіпертензією на фоні ХОЗЛ у поєднанні з гіпертонічною хворобою під впливом лікування

Chronic obstructive pulmonary disease significantly affects the quality of life, considerably limiting the physical capabilities of patients and is one of the main causes of morbidity and mortality in modern society. Currently, the problem of the comorbidity for the patients with chronic obstructive pulmonary disease is very relevant. The most common in patients of this category is hypertension. Today, it has been established that disorders in the immune system are detected in a very large group of diseases, including both chronic obstructive pulmonary disease and hypertension. The purpose of the study was to evaluate the dynamics of inflammatory markers in the patients with pulmonary hypertension on the background of chronic obstructive pulmonary disease in combination with hypertension under the influence of treatment. Material and methods. The results of the study are based on data from a comprehensive survey of 170 patients aged 40 to 65 years with chronic obstructive pulmonary disease, of which 123 had pulmonary hypertension (of which 87 had stage II hypertension and 36 were without hypertension) and 47 people were without pulmonary hypertension. The patients were chosen in the period from 2015 to 2018 on the basis of the municipal institution "Zaporizhzhia regional clinical hospital" of the Zaporizhzhia regional council. Results and discussion. The results of this study indicate the role of inflammation, or rather the levels of hs-CRP and IL-6, in the pathogenesis of pulmonary hypertension in patients with chronic obstructive pulmonary disease. The level of hs-CRP among the patients with pulmonary hypertension on a background of chronic obstructive pulmonary disease made up 10.46 [6,24 ; 15,30] mg/l and was significantly higher as against the values in the group of patients with chronic obstructive pulmonary disease without pulmonary hypertension and compared with group of healthy persons. The increase in the level of IL-6 in the group of patients having pulmonary hypertension with chronic obstructive pulmonary disease is significantly higher by 57 % compared to the value in the group of chronic obstructive pulmonary disease without pulmonary hypertension and by 7.4 times the value in the group of healthy individuals (p <0.05). Comparing the subgroups of patients, and depending on the variant of exacerbation of chronic obstructive pulmonary disease, the level of hs-CRP and IL-6 was considerably higher in the subgroup with the infectious type of exacerbation compared with the subgroup of the non-infectious type of exacerbation of chronic obstructive pulmonary disease. Conclusion. After 12 months of treatment, when roflumilast was added to the basic therapy, we revealed a statistically significant difference in the levels of IL-6, hs-CRP and IL-10 in the plasma of patients with pulmonary hypertension on the background of chronic obstructive pulmonary disease combined with hypertension

Association between hydrogen sulfide and OSA-associated hypertension: a clinical study.

We sought to unravel the role of hydrogen sulfide (H2S) in the development of hypertension in patients with obstructive sleep apnea (OSA). The study sample included 80 patients with OSA and 45 healthy controls. All subjects underwent measurement of blood pressure (BP) and serum H2S level in the morning. Twentynine of the 39 patients with OSA and concomitant hypertension and 23 of the 41 patients with OSA but no concomitant hypertension received continuous positive alveolar pressure (CPAP) therapy for 4 weeks. Twenty-four-hour ambulatory BP and serum H2S were determined before and after CPAP. Respiratory indices including apnea hypopnea index (AHI), lowest oxygen saturation (SaO2), and length of time < 90% saturated (T90) were determined by polysomnography. Associations between H2S, BP, respiratory indices, and changes with CPAP were analyzed. OSA patients had significantly higher systolic BP (p = 0.003) and diastolic BP (p = 0.009) and lower H2S levels (p = 0.02) compared to healthy controls. H2S negatively correlated with AHI (p = 0.005), T90 (p = 0.009), morning systolic BP (p = 0.02), and morning diastolic BP (p = 0.03). All respiratory indices were significantly improved (p < 0.05) after CPAP in OSA patients with or without hypertension. BP was significantly reduced and H2S significantly increased after CPAP in OSA patients with hypertension (p < 0.05) but not in OSA patients without hypertension (p > 0.05). Multivariate linear regression analysis demonstrated that 24h systolic BP and 24h diastolic BP correlated with H2S as well as their changes after CPAP treatment. Reduction in H2S may play a role in the pathogenesis of hypertension in patients with OSA.

Hypertension in malignancy-an underappreciated problem.

Hypertension is one of the most common comorbidities in cancer patients with malignancy, in particular, in the elderly. On the other hand, hypertension is a long-term consequence of antineoplastic treatment, including both chemotherapy and targeted agents. Several chemotherapeutics and targeted drugs may be responsible for development or worsening of the hypertension. The most common side effect of anti-VEGF (vascular endothelial growth factor) treatment is hypertension. However, pathogenesis of hypertension in patients receiving this therapy appears to be associated with multiple pathways and is not yet fully understood. Development of hypertension was associated with improved antitumor efficacy in patients treated with anti-antiangiogenic drugs in some but not in all studies. Drugs used commonly as adjuvants such as steroids, erythropoietin stimulating agents etc, may also cause rise in blood pressure or exacerbate preexisiting hypertension. Hypotensive therapy is crucial to manage hypertension during certain antineoplastic treatment. The choice and dose of antihypertensive drugs depend upon the presence of organ dysfunction, comorbidities, and/or adverse effects. In addition, severity of the hypertension and the urgency of blood pressure control should also be taken into consideration. As there are no specific guidelines on the hypertension treatment in cancer patients we should follow the available guidelines to obtain the best possible outcomes and pay the attention to the individualization of the therapy according to the actual situation.

UNIFFERENTIATED CONNECTIVE TISSUE DYSPLASIA AS A POTENTIAL PREDICTOR OF ARTERIAL HYPERTENSION DEVELOPMENT IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

The article presents the results of studies of markers of connective tissue dysplasia and the content of the main fibroblast growth factor in blood plasma in patients with type 2 diabetes. The presence of significant correlations between the studied parameters with the occurrence and progression of hypertension in patients with type 2 diabetes is established. A regression model for predicting the development of arterial hypertension is proposed in patients with diabetes mellitus. The development of hypertension in patients with DM type 2 in combination with UCTD occurs earlier, is almost independent of the duration of diabetes, more pronounced hypertension is observed in patients with visceral and skeletal symptoms of UCTD. This is evidence of the role of UCTD in the pathogenesis of hypertension in patients with type 2 diabetes. Essential role in the emergence and progression of hypertension in patients with DM type 2 is played by metabolic disorders of the connective tissue that manifests as clinical signs of UCTD. FGF2, which content is increased in patients with visceral and/or skeletal symptoms of UCTD, is involved in its pathogenesis. The regression model of the prediction of hypertension in patients with DM type 2 with an assessment of the presence of UCTD signs and the duration of diabetes has a high prognosticity, specificity and sensitivity, which makes it possible to apply this method in clinical practice to determine patients with high risk of development of hypertension.

The role of CYP11B2 polymorphism in the pathogenesis of hypertension in patients with adrenal incidentaloma

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Renal denervation enhances GABA-ergic input into the PVN leading to blood pressure lowering in chronic kidney disease

Sympathoexcitation plays an important role in the pathogenesis of hypertension in patients with chronic kidney disease (CKD). The paraventricular nucleus of the hypothalamus (PVN) in the brain controls sympathetic outflow through γ-amino butyric acid (GABA)-ergic mechanisms. Renal denervation (RDN) exerts a long-term antihypertensive effect in hypertension with CKD; however, the effects of RDN on sympathetic nerve activity and GABA-ergic modulation in the PVN are not clear. We aimed to elucidate whether RDN modulates sympathetic outflow through GABA-ergic mechanisms in the PVN in hypertensive mice with CKD. In 5/6-nephrectomized male Institute of Cancer Research mice (Nx) at 4 weeks after nephrectomy, systolic blood pressure (SBP) was significantly increased, accompanied by sympathoexcitation. The Nx-mice underwent RDN or sham operation, and the mice were divided into three groups (Control, Nx-Sham, and Nx-RDN). At 2 weeks after RDN, SBP was significantly decreased and urinary sodium excretion was increased in Nx-RDN compared with Nx-Sham. Urinary norepinephrine excretion (uNE) levels did not differ significantly between Nx-RDN and Nx-Sham. At 6 weeks after RDN, SBP continued to decrease and uNE levels also decreased in Nx-RDN compared with Nx-Sham. Bicuculline microinjection into the PVN increased mean arterial pressure and lumbar sympathetic nerve activity in all groups. The pressor responses and change in lumbar sympathetic nerve activity were significantly attenuated in Nx-Sham, but were enhanced in Nx-RDN at 6 weeks after RDN. The findings from the present study indicate that RDN has a prolonged antihypertensive effect and, at least in the late phase, decreases sympathetic nerve activity in association with enhanced GABA-ergic input into the PVN in mice with CKD.

High Frequency of Arterial Hypertension in Patients After Liver Transplantation

BackgroundCardiovascular diseases are among the most frequent causes of patient death after liver transplantation. The aim of this retrospective clinical study was to estimate the prevalence of arterial hypertension among patients after successful liver transplantation and the role of immunosuppressive drugs in the pathogenesis of hypertension in these patients. Patients and MethodsA total of 88 patients (age 47 .5 ± 12.1 years; 33 women and 55 men) who had undergone successful liver transplantation and completed 24 months follow-up were studied. The results are presented as means with standard deviations. ResultsAt 1, 12, and 24 months after liver transplantation, the prevalences of hypertension were 44.3%, 54.5%, and 62.5%, respectively. Systolic and diastolic blood pressure in these months were 124.1 ± 14.8, 132.8 ± 19.1, and 135.2 ± 17.3 mm Hg and 83.3 ± 12.0, 87.3 ± 11.1, and 87.9 ± 11.1 mm Hg, respectively. The estimated glomerular filtration rates were 77.8 ± 32.3, 80.3 ± 30.8, and 78.8 ± 29.1 mL/min/1.73 m2, respectively. Arterial hypertension was significantly more frequent in patients treated with cyclosporine A than in those treated with tacrolimus (P = .004) or everolimus (P = .005). In patients treated with tacrolimus, a positive correlation was found between tacrolimus blood concentration and systolic blood pressure (R = 0.34; P = .01) and a negative correlation was found between estimated glomerular filtration rate and systolic blood pressure (R = −0.28; P = .02). ConclusionsBased on study findings, the following conclusions were drawn: arterial hypertension occurs in more than 50% of patients after liver transplantation (significantly higher frequency than in the general population); calcineurin inhibitors may participate in the pathogenesis of arterial hypertension in patients after successful liver transplantation; and the clinical importance of these findings and the influence on cardiovascular outcome of the liver transplant recipients need further investigation.

A unifying mechanism for WNK kinase regulation of sodium-chloride cotransporter.

Mammalian with-no-lysine [K] (WNK) kinases are a family of four serine-threonine protein kinases, WNK1-4. Mutations of WNK1 and WNK4 in humans cause pseudohypoaldosteronism type II (PHA2), an autosomal-dominant disease characterized by hypertension and hyperkalemia. Increased Na(+) reabsorption through Na(+)-Cl(-) cotransporter (NCC) in the distal convoluted tubule plays an important role in the pathogenesis of hypertension in patients with PHA2. However, how WNK1 and WNK4 regulate NCC and how mutations of WNKs cause activation of NCC have been controversial. Here, we review current state of literature supporting a compelling model that WNK1 and WNK4 both contribute to stimulation of NCC. The precise combined effects of WNK1 and WNK4 on NCC remain unclear but likely are positive rather than antagonistic. The recent discovery that WNK kinases may function as an intracellular chloride sensor adds a new dimension to the physiological role of WNK kinases. Intracellular chloride-dependent regulation of WNK's may underlie the mechanism of regulation of NCC by extracellular K(+). Definite answer yet will require future investigation by tubular perfusion in mice with altered WNK kinase expression.

Angiotensin Blockade in Late Autosomal Dominant Polycystic Kidney Disease

BackgroundHypertension develops early in patients with autosomal dominant polycystic kidney disease (ADPKD) and is associated with disease progression. The renin–angiotensin–aldosterone system (RAAS) is implicated in the pathogenesis of hypertension in patients with ADPKD. Dual blockade of the RAAS may circumvent compensatory mechanisms that limit the efficacy of monotherapy with an angiotensin-converting–enzyme (ACE) inhibitor or angiotensin II–receptor blocker (ARB).MethodsIn this double-blind, placebo-controlled trial, we randomly assigned 486 patients, 18 to 64 years of age, with ADPKD (estimated glomerular filtration rate [GFR], 25 to 60 ml per minute per 1.73 m2 of body-surface area) to receive an ACE inhibitor (lisinopril) and placebo or lisinopril and an ARB (telmisartan), with the doses adjusted to achieve a blood pressure of 110/70 to 130/80 mm Hg. The composite primary outcome was the time to death, end-stage renal disease, or a 50% reduction from the baseline estimated GFR. Secondary outcomes included the rates of change in urinary aldosterone and albumin excretion, frequency of hospitalizations for any cause and for cardiovascular causes, incidence of pain, frequency of ADPKD-related symptoms, quality of life, and adverse study-medication effects. Patients were followed for 5 to 8 years.ResultsThere was no significant difference between the study groups in the incidence of the composite primary outcome (hazard ratio with lisinopril–telmisartan, 1.08; 95% confidence interval, 0.82 to 1.42). The two treatments controlled blood pressure and lowered urinary aldosterone excretion similarly. The rates of decline in the estimated GFR, urinary albumin excretion, and other secondary outcomes and adverse events, including hyperkalemia and acute kidney injury, were also similar in the two groups.ConclusionsMonotherapy with an ACE inhibitor was associated with blood-pressure control in most patients with ADPKD and stage 3 chronic kidney disease. The addition of an ARB did not alter the decline in the estimated GFR. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; HALT-PKD [Study B] ClinicalTrials.gov number, NCT01885559.)

Melatonin ameliorates endothelial dysfunction, vascular inflammation, and systemic hypertension in rats with chronic intermittent hypoxia

The pathogenesis of hypertension in patients with obstructive sleep apnea (OSA) is associated with endothelial dysfunction induced by chronic intermittent hypoxia (IH). Studies have shown that administration of melatonin ameliorates oxidative injury and inflammation. This study examined the effect of melatonin on the oxidative stress, endothelial dysfunction, and inflammation during the pathogenesis of hypertension in chronic IH. Adult Sprague-Dawley rats that had received a daily injection of melatonin or vehicle were exposed to IH treatment mimicking a severe OSA condition for 14-21days. Systolic pressure was significantly higher in the vehicle-treated (144±2.7mmHg) but not in the melatonin-treated rats (123±5.1mmHg) by 21-day IH treatment when compared with the normoxic control. Levels of malondialdehyde and the expressions of NADPH oxidase, pro-inflammatory mediators (TNF-α, inducible NO synthase, COX-2), and adhesion molecules (ICAM-1, VCAM-1, and E-selectin) of the thoracic aorta were markedly increased by 14-day IH treatment preceding the hypertensive response. Also, levels of nitric oxide (NO˙), endothelial-dependent relaxation, and the expressions of endothelial NO synthase (eNOS) and antioxidant enzymes (GPx, CAT, and Cu/Zn SOD) were significantly lowered in the IH rats. Melatonin treatment significantly mitigated the increased expression of NADPH oxidase, pro-inflammatory mediators, and adhesion molecules. Moreover, melatonin prevented the endothelial dysfunction with ameliorated levels of NO˙, endothelial-dependent relaxation, and expressions of eNOS and antioxidant enzymes. These results suggest that melatonin is protective against IH-induced hypertension and endothelial dysfunction via an antioxidant and anti-inflammatory mechanism.

The Effect of Sodium Restricted Diet on Plasma Visfatin Levels in Hypertensive Patients with Visceral Obesity

Aim/Background: Experimental and clinical studies revealed contradictory data concerning the influence of renin-angiotensin-aldosterone (RAA) system activation on visfatin release. The aim of the present study was the assessment of the effect of dietary sodium restriction with RAA system activation on visfatin level in hypertensive and normotensive patients with visceral obesity. Methods: The study included 24 hypertensive patients with visceral obesity (12 women) and 22 normotensive subjects with visceral obesity (11 women) constituting the control group. Plasma renin activity, plasma insulin, aldosterone and visfatin levels were determined twice, on normal-salt diet after 6-8 h in recumbent position and the second time after 3 days of dietary sodium restriction and upright position for 2 h. Dietary compliance was controlled by 24 h natriuresis measurement. Results: Hypertensive patients had significantly higher plasma visfatin level than the control group [11.0 (8.5-13.5) vs. 6.8 (6.0-7.6) ng/ml, p=0.003]. Dietary sodium restriction and upright position caused significant increase in PRA and plasma aldosterone level in both groups. While, plasma visfatin level remained unaffected. In the combined group plasma visfatin levels correlated with BMI (r=0.398), waist circumference (r=0.391), glucose (r=0.328), insulin (r=0.663), HOMA-IR (r=0.698), triglycerides (r=0.500) and CRP (r=0.546) but not with percentage of fat mass, percentage of trunk fat, and blood pressure values. Conclusions: 1) Increased plasma visfatin concentration may play a significant role in the pathogenesis of hypertension in patients with visceral obesity. 2) RAA system activation by dietary sodium restriction and upright position has no effect on plasma visfatin levels in subjects with visceral obesity.

Pathogenesis of hypertension in patients with primary hypothyroidism

Objective. To investigate short-term effects of thyroxin replacement therapy on blood pressure (BP), left ventricular mass index (LVMI), interstitial fluid volume (IFV) and skin vessels resistance in patients with first diagnosed primary hypothyroidism (PH) and past history of arterial hypertension (AH). Design and methods. 49 patients with PH and AH were examined twice: before the therapy onset and after euthyroid state was achieved. All patients underwent daily BP monitoring, echocardiography, body integral rheography and high frequency ultrasound dopplerography of nail ridge arterioles. Results. Decrease in daytime systolic BP by 8.5 (95 % CI: 5.5-11.5) mm Hg, nighttime systolic BP by 5.3 (2.5-8.1) mm Hg, daytime diastolic BP by 3.8 (1.2-6.4) mm Hg, nighttime diastolic BP by 3.5 (0.9-6.1) mm Hg, IFV by 1.5 (0.11-2.91) l, LVMI by 8.5 (1.9-15.0) g/m 2 and Purselo index by 0.19 (0.05-0.33) units (or 25 % to initial level) were found in patients with PH when euthyroid state was achieved. Conclusion. IFV can play a key role in AH development in patients with PH.

Renalase, a Novel Enzyme Involved in Blood Pressure Regulation, Is Related to Kidney Function but Not to Blood Pressure in Hemodialysis Patients

Renalase, secreted by the kidney, degrades catecholamines and may play a role in the regulation of sympathetic tone and blood pressure. The aim of this study was to assess serum renalase levels in hemodialysis patients and their relationship to blood pressure control, type of antihypertensive therapy and the presence of residual renal function. Results: The mean serum renalase in the study cohort was significantly higher than in the control group (27.53 ± 7.18 vs. 3.86 ± 0.73 µg/ml, p < 0.001). The serum renalase concentration was significantly lower in patients with residual renal function when compared to the anuric patients. The type of hypotensive treatment (β-blockers, ACE inhibitors or AT1 receptor blockers) did not affect renalase levels. There was a significant inverse correlation between the serum renalase and age (r = –0.28, p = 0.023) and residual renal function (r = –0.327, p = 0.001). Renalase was not related to blood pressure, heart rate or hemodialysis vintage. Conclusion: Elevated renalase levels in HD patients may be due to impaired kidney function. Further studies are needed to prove or disprove the possible role of renalase in the pathogenesis of hypertension in patients with kidney diseases.

Effect of successful parathyroidectomy on 24-hour ambulatory blood pressure in patients with primary hyperparathyroidism

Objective The pathogenesis of hypertension in patients with primary hyperparathyroidism (PHPT) is unclear, and the prevailing opinion is that parathyroidectomy does not affect the blood pressure (BP). Most previous studies have been based on BP measurements at rest in a clinical setting. The aim of this study was to get additional information by 24-hour ambulatory measurements. Design and patients Forty-nine consecutive patients with PHPT (age 63 ± 12 years, 44 women) were examined before and 6 months after curative parathyroid surgery. Measurements Serum concentrations of calcium and PTH, and 24-hour ambulatory mean, minimum, and maximum systolic (S) and diastolic BP, and mean arterial BP. Results On average, the patients showed no BP change after parathyroidectomy. However, those with a history of hypertension ( n = 20) showed generally increased BP values after parathyroidectomy, with significantly increased minimum and average SBP ( P = 0.02 and P = 0.04, respectively), whereas patients without a history of hypertension ( n = 29) showed unchanged or slightly reduced BP values after parathyroidectomy, with significantly decreased maximum SBP ( P = 0.04). Serum concentrations of PTH and calcium were not significantly related to any of the BP variables measured. Conclusions The novel finding that patients with both PHPT and hypertension may show increased BP after parathyroidectomy warrants intensified BP control postoperatively in these patients, and motivates early treatment of PHPT in order to prevent the development of complicating hypertension.

Hyperresistinemia Is Associated With Coexistence of Hypertension and Type 2 Diabetes

Numerous studies have demonstrated that high blood pressure substantially increases the risk of microvascular and macrovascular complications in patients with type 2 diabetes mellitus (T2DM). Currently, we found that serum resistin, an adipocyte- and monocyte-derived cytokine, was positively correlated with several components of the metabolic syndrome, including hypertension in T2DM. To investigate the association of resistin with an etiologic difference among subjects with hypertension with T2DM, hypertension without T2DM, and normotensive T2DM, we analyzed 210 subjects, including 91 with hypertension with T2DM, 55 with hypertension without T2DM, and 64 with normotensive T2DM. Serum resistin level was higher in subjects with hypertension with T2DM, followed by subjects with normotensive T2DM and hypertension without T2DM, irrespective of antihypertensive treatment status (20.9+/-17.6 and 14.0+/-8.9 versus 11.2+/-7.6 ng/mL, respectively; P<0.01). Simple regression analysis revealed that resistin positively correlated with blood pressure (systolic blood pressure: r=0.29, P<0.01; diastolic blood pressure: r=0.21, P<0.05) and intima-media thickness (r=0.27; P<0.05) in patients with T2DM but not in subjects with hypertension without T2DM. Multiple regression analysis, adjusted for age, gender, body mass index, fasting glucose, high-density lipoprotein cholesterol, white blood cell counts, and glomerular filtration rate, further revealed that resistin was an independent factor for high blood pressure in patients with T2DM (P<0.05). In vitro gene expression analysis in human coronary endothelial cells revealed that resistin induced fatty acid binding protein, a key molecule of insulin resistance, diabetes, and atherosclerosis. These results suggest that hyperresistinemia would contribute to the pathogenesis of hypertension in patients with T2DM, significantly linked to vascular complications and cardiovascular events.

Endothelin-1 and Nitric Oxide in Patients on Chronic Hemodialysis

Aim. To establish the role of endothelin-1 and nitric oxide in the pathogenesis of hypertension in patients on chronic aemodyalisis by correlating endothelin-1 and NO plasma concentrations to the level of arterial hypertension with respect to angiotensin-converting enzyme (ACE) inhibitor therapy. Methods. We determined plasma concentrations of endothelin-1 and NO in patients on chronic hemodialysis (CHD) before and after hemodialysis treatment. The study included 30 CHD patients and 20 healthy participants as controls. Correlation to blood pressure was determined, as well as the effect of ACE inhibitors on the relationship between both endothelin-1 and NO in correlation with arterial hypertension. Main findings.Endothelin-1 plasma concentration was significantly higher in CHD patients before hemodialysis treatment than in healthy controls. Endothelin-1 plasma concentration was also significantly higher in CHD patients after hemodialysis than in healthy controls. There was a significant decrease in endothelin-1 plasma concentration after hemodialysis in comparison with its values before hemodialysis. In CHD patients, a positive correlation was found between endothelin-1 plasma concentration and systolic blood pressure after hemodialysis, irrespective of ACE inhibitors therapy. In CHD patients taking ACE inhibitors, systolic blood pressure increased with increasing endothelin-1 plasma concentration before as well as after hemodialysis. In patients taking ACE inhibitors, there was a tendency for diastolic blood pressure to increase with an increase in endothelin-1 plasma concentration after hemodialysis and to decrease with an increase in NO plasma concentration. Conclusion. NO and endothelin-1 play a significant role in etiology of the hemodynamic changes of blood pressure during the dialysis.

Abnormal nocturnal plasma level of vasopressin and aldosterone in obstructive sleep apnea syndrome

Hypertension is common among patients with obstructive sleep apnea syndrome (OSAS). The mechanisms causing blood pressure elevation are not clarified, but there may be an increased activity in the vasoactive hormonal systems due to numerous hypoxic episodes during the night. The purpose of the study was to measure plasma concentrations of vasopressin (AVP), endotheline (Endot), angiotensin II (Ang II), and aldosterone (Aldo) during the night in patients with OSAS and healthy controls. We wanted to test the hypothesis that patients with OSAS have an abnormal plasma level of vasoactive hormones during night. Fourteen patients with an apnea-hypopnea index higher than 10, and 9 healthy control subjects were included in the study. Blood samples were drawn every second hour from 2030h to 0630h for measurement of AVP, Endot, Ang II, Aldo. Oxygen saturation was recorded continuously. Blood pressure and heart rate were measured immediately before blood sampling. Hormones were determined by radioimmunoassay. AVP was significantly increased in patients with OSAS compared with healthy control subjects during the night (OSAS: 0.70 pg/ml (mean), healthy controls: 1.33 pg/ml, p<0.05). Endot did not differ between patients and controls. Aldo increased during the night in patients with OSAS and was elevated at the end of the night, whereas Ang II was the same in the two groups. The observed time with oxygen saturation below 90% were significantly higher in patients with OSAS than in controls (10.6% versus 0,8%, p<0.01). Patients with OSAS had a higher blood pressure, both systolic and diastolic, compared with healthy control subjects (147/89 versus 127/78, p<0.05/p<0.05). It is concluded that patients with obstructive sleep apnea syndrome have an abnormal nocturnal rhythm in plasma concentrations of vasopressin and aldosterone. It is suggested that increased activity in these hormones is involved in the pathogenesis of hypertension in patients with OSAS.

Obstructive sleep apnea and hypertension: are peripheral chemoreceptors involved?

The mechanism of pathogenesis of hypertension in patients with obstructive sleep apnea (OSA) is unknown. Many investigators point to the high sympathetic nervous system activity (SNS) observed in OSA patients. However, there is no clear explanation as to the mechanism for the development of SNS hyperactivity in these patients. A common feature of patients with OSA is repetitive bouts of transient hypoxemia during sleep. Repetitive transient hypoxemia in rats has resulted in hypertension. In OSA patients, resolution of nocturnal hypoxemia with CPAP has corrected nocturnal and diurnal hypertension. Also, exposure to hyperoxia reduces blood pressure and sympathetic activity in OSA patients, but not in normals. These data suggest a significant role of peripheral chemoreceptors in the regulation of vascular tone. We hypothesize that peripheral chemoreceptors significantly contribute to the pathogenesis of hypertension in patients with OSA and that this is associated with chemoreceptor hyperactivity. This implies that correcting the intermittent nocturnal hypoxemia alone may prevent the cardiovascular morbidity associated with obstructive sleep apnea.

The potent role of increased sympathetic tone in pathogenesis of essential hypertension with neurovascular compression.

To study the role of increased sympathetic tone in pathogenesis of hypertension in patients with essential hypertension with neurovascular compression. Twenty-three patients with essential hypertension, 13 patients with secondary hypertension, and 46 normotensive subjects were investigated. Neurovascular compression was evaluated by MRT. The power spectral components of heart rate variability as indices of autonomic nerve tone were determined to investigate the possibility that sympathetic tone mediates the neurovascular compression-induced increase in blood pressure. Neurovascular compression of the rostral ventrolateral medulla (RVLM) was observed in 70% of essential hypertension group, none of secondary hyperension group and 16% of normotensive group (P < 0.001). The age-adjusted low-frequency power spectral density (A-PSD) (0.04 to 0.15 Hz), which is an index of sympathetic tone, was significantly higher in patients with essential hypertension (139.5 +/- 6.7%) with neurovascular compression than in essential hypertension patients without neurovascular compression (92.2 +/- 6.8%), normotensive subjects with (102.8 +/- 13.0%) and without neurovascular compression (100.1 +/- 4.1%), and patients with secondary hypertension (95.7 +/- 10.2%) (P < 0.001). There was no significant difference in the high-frequency A-PSD (0.15 to 0.40 Hz), which is an index of vagal tone, among groups. Neurovascular compression was not always associated with an increase in sympathetic nerve tone. Hypertension was present in subjects with neurovascular compression, who had increased sympathetic tone but not in those with normal sympathetic tone. An increase in sympathetic tone may mediate the neurovascular compression-induced increase in blood pressure. Journal of Human Hypertension (2000) 14, 807-811

Insulin levels during fasting and the glucose tolerance test and Homa's index predict subsequent development of hypertension.

To determine whether there is a longitudinal relationship between hypertension and hyperinsulinemia and to find the most useful parameter(s) for predicting the subsequent development of hypertension. The oral glucose (75 g) tolerance test (OGTT) was performed in 313 patients, who were divided into three groups according to glucose tolerance based on the WHO criteria: normal, borderline and diabetes mellitus. The fasting insulin (IRI) levels, sigmaIRI (the sum of the insulin levels 0, 30, 60 and 120 min after the OGTT), insulinogenic index and Homa's index, a candidate for the simple assessment of insulin sensitivity, of the normotensive and hypertensive subjects in each subgroup were compared. In addition, 145 normotensive subjects were followed up for over 3 years and observed for the development of hypertension. Hypertensive diabetic subjects had not only higher fasting IRI levels and sigmaIRI values, but they also had higher Homa's indices than normotensive diabetics. Normotensive subjects with normal glucose tolerance (n = 20) did not develop hypertension. However, 16 out of 94 patients with borderline glucose tolerance and five out of 31 diabetics became hypertensive. The incidence of hypertension in the group with fasting IRI > or = 15, sigmaIRI > or = 150 or Homa's index > or = 4 was between 5 and 9 times higher than that in the group with fasting IRI < 10, sigmaIRI < 100 or Homa's index < 2. This difference was still significant when multivariate analysis, including various factors such as age, body mass index (BMI) and sex, was performed. These results suggest that higher plasma IRI levels and/or insulin resistance are closely related to the pathogenesis of hypertension in patients with diabetes mellitus. Homa's index, fasting and sigmaIRI may be useful predictors of the subsequent development of hypertension.