Development Of Hypertension In Patients Research Articles

Impaired endothelium-dependent vasodilation does not initiate the development of sunitinib-associated hypertension.

Tyrosine kinase inhibitors targeting angiogenesis have become an important part of the treatment of patients with several types of cancer. One of the most reported side effects of vascular endothelial growth factor receptor (VEGFR)-targeted therapies is hypertension. In this study, we hypothesized that the development of hypertension in patients treated with sunitinib, a multitargeted tyrosine kinase inhibitor, is preceded by reduced endothelium-dependent vasodilation. Moreover, we hypothesized that this endothelial dysfunction is a result of impaired nitric oxide release. In a placebo-controlled experiment, we determined vascular responses in isolated mesenteric arteries of rats (n = 26) after 7 days of sunitinib treatment. Sunitinib reduced endothelium-dependent vasodilation, but not endothelium-independent vasodilation. Moreover, we observed that the difference in endothelium-dependent vasodilation between controls and sunitinib-treated animals disappeared in the presence of N-nitro-L-arginine methyl ester (L-NAME), a nitric oxide antagonist. In patients with metastatic renal cell carcinoma, before and 1 week after start of sunitinib, the endothelium-dependent vasodilator response to intra-arterial acetycholine and the endothelium-independent vasodilator response to intra-arterial sodium nitroprusside was assessed with venous occlusion plethysmography. No changes in forearm blood flow ratios were observed. Mean arterial pressure did significantly increase from 101.9 ± 3.8 to 106.1 ± 2.6 mmHg after 1 week and further to 115.8 (±4.9) mmHg after 2 weeks of treatment. In animals, this study confirms that exposure to high concentrations of sunitinib reduces endothelium-dependent vasodilation by reducing endothelial release of nitric oxide. In humans, however, reduced endothelium-dependent vasodilation does not precede the development of hypertension in patients treated with sunitinib.

The association between systolic blood pressure and positional changes of the main renal venous blood flow

Objective. To assess the impact of the position-dependent changes of the main renal venous blood flow on systolic blood pressure (SBP). Design and methods. We measured blood pressure, blood flow in the renal veins, and resistance index in patients with pathological kidney mobility (PKM). Based on the difference between the maximum and minimum velocity of renal venous blood flow several groups were identified, namely, groups with normal venous blood flow, with borderline and severe alterations of venous outflow. Based on the sum of the rotation angles (according to the excretory urogram and ultrasonography wedge and tilt test in three planes), patients were divided into three groups: I rotation degree — sum of rotation angles 40°, II — from 40° to 70°, III — 70° and above. Results. We found a relation between SBP and both velocity and resistance indices in both renal vessels. There is an increase in the incidence and amplitude of SBP fluctuations in patients with all rotation degrees with the direct association with the severity of PKM. The classification of PKM patients based on the sum of rotation angles measured by ultrasound and Doppler examinations is highly efficient, and the accuracy was 89,13%. Conclusions. The changes in renal veins seem to contribute to the SBP elevation. The measurement of BP in six static states can enable new insight on the physiological BP changes and will help early diagnostics and verification of pathogenic factors responsible for the development of hypertension in patients with PKM and position-dependent changes of the main renal venous flow.

Peculiarity of medical management of patients with arterial hypertension after liver transplantation

The article analyzes information of the prevalence, causes and mechanisms of development of hypertension in patients after liver transplantation. The authors integrate data from domestic and foreign literature about priorities of choice of antihypertensive drugs and possible changes in patterns of immunosuppressive drug therapy to reduce the risk of onset and progression of cardiovascular disease in patients who were underwent orthotopic liver transplantation.

Clinical risk factors for the development of hypertension in patients treated with inhibitors of the VEGF signaling pathway.

VEGF signaling pathway inhibitor (anti-VEGF) therapy is associated with hypertension, but little is known about predisposing clinical characteristics. This study describes the real-world association between baseline clinical characteristics, blood pressure (BP) response, and survival in patients prescribed anti-VEGF therapies. Clinical data from Partners HealthCare in Massachusetts was obtained from adults treated with anti-VEGF therapies (2002-2013). Treatment-induced hypertensive response was defined as worsening of preexisting hypertension or new diagnosis of hypertension (if no prior hypertension history). Data from 1120 patients with renal cell carcinoma (32.2%), hepatocellular carcinoma (11.6%), gastrointestinal stromal tumors (12.5%), and other sarcomas (15.3%) were analyzed. Most patients received sunitinib (52%), sorafenib (25.9%), or pazopanib (18%). A treatment-induced hypertensive response was identified in 49.7% of treated patients. Preexisting hypertension, present in 65.4%, was an independent risk factor for BP elevation (odds ratio [OR], 1.56; 95% confidence interval [CI], 1.27-1.92); other risk factors included age ≥60 years (OR, 1.26; 95% CI, 1.06-1.52), and body mass index (BMI) ≥25 kg/m(2) (OR, 1.26; 95% CI, 1.04-1.53). Race, sex, anti-VEGF therapy prescribed, and baseline antihypertensive class were not significant risk factors. The absolute observed mean increase in BP was 21 mm Hg (systolic)/15 mm Hg (diastolic), both in patients with and without preexisting hypertension. The development of hypertension predicted improved survival (hazard ratio, 0.76; 95% CI, 0.65-0.89). Preexisting hypertension, age, and BMI identify patients at risk for significant anti-VEGF therapy-induced BP elevation. Hypertension appears to be a clinical biomarker of efficacy of anti-VEGF therapies in a broad range of malignancies.

Blood pressure, fludrocortisone dose and plasma renin activity in children with classic congenital adrenal hyperplasia due to 21‐hydroxylase deficiency followed from birth to 4 years of age

Infants with congenital adrenal hyperplasia (CAH) require higher doses of fludrocortisone (FC) due to physiological mineralocorticoid resistance. The adequacy of mineralocorticoid replacement should be closely monitored to avoid hypertension. To evaluate blood pressure (BP) in infants with CAH due to 21-hydroxylase deficiency. Thirty-three patients (18f/15m) diagnosed by newborn screening were followed until the age of 4years. Mean start of HC and FC treatment was day 9·8±9·2 postnatally. Mean daily HC dose ranged from 8·6 to 12·3mg/m(2) /day. During the first year of life prevalence of systolic hypertension was up to 45·5%. At 12 and at 18months, BP was highest. Prevalence of systolic hypertension was up to 57·6% at 18months of age. After 24months BP levels were lower and at 48months prevalence of hypertension decreased to 15·2%. Systolic and diastolic BP correlated significantly with the administered fludrocortisone dose (r=0·3, P=0·005), but not with body mass index. Hypertensive children received significantly higher FC doses and had significantly lower plasma renin activity during the study period. High prevalence of transient, most likely FC induced hypertension was found in young children with classic CAH diagnosed by newborn screening. The changing mineralocorticoid sensitivity in infants is a risk factor for the development of hypertension in patients with CAH, who are treated with FC. Therefore suppressed plasma renin activity should be avoided to prevent arterial hypertension.

Clinicopathologic factors associated with the development of sunitinib induced hypertension (HTN) in patients (pts) with metastatic renal cell carcinoma (mRCC).

508 Background: The VEGFR inhibitor sunitinib is a standard treatment for metastatic renal cell carcinoma (mRCC). HTN, an on-target class effect of VEGF signaling-pathway inhibitors, has been shown to correlate with clinical outcome. Studies have shown the association between genetic polymorphisms in several genes, and the development of HTN in patients treated with targeted therapies. We aimed to study the association between readily available clinicopathologic factors and the development of sunitinib induced HTN in mRCC patients. Methods: Records from mRCC patients treated with sunitinib in 9 centers across 2 countries were retrospectively reviewed. Sunitinib induced HTN was defined as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg. Analysis of the association between clinicopathologic factors and the development of HTN was performed using logistic regression. Results: Between 2004-2013, 302 patients with mRCC were treated with sunitinib. The incidence of sunitinib induced HTN was 50% (n=152). Clinicopathologic factors included in the analysis were age (median 63), gender (67% male), HENG risk (good 22%, intermediate 59%, poor 19%), smoking status (active 21%), BMI (obese=BMI ≥30, 28%; overweight=BMI 25-29.9, 37%; normal weight= BMI <25, 35%), pre-treatment HTN (58%), past nephrectomy (83%), histology (73% clear cell), > 1 metastatic site (82%), metastatic site (lung 72%, liver 25%, bones 40%), pre-treatment neutrophil to lymphocyte ratio (>3 in 45%), treatment line (first vs advanced), sunitinib dose reduction/treatment interruption (45%). Absence of liver metastases (OR 3.5, p=0.02), pre-treatment neutrophil to lymphocyte ratio ≤ 3 (OR 5.5, p=0.001), and BMI (overweight and normal weight vs obese, OR 2.2 and 2.3 respectively, p=0.01 both) were independently associated with the development of HTN. Conclusions: In metastatic renal cell carcinoma patients treated with sunitinib, readily available clinicopathologic factors may be used to identify patients who are prone to the development of HTN.

Особенности ведения пациентов с артериальной гипертензией после трансплантации печени

The article analyzes information of the prevalence, causes and mechanisms of development of hypertension in patients after liver transplantation. The authors integrate data from domestic and foreign literature about priorities of choice of antihypertensive drugs and possible changes in patterns of immunosuppressive drug therapy to reduce the risk of onset and progression of cardiovascular disease in patients who were underwent orthotopic liver transplantation.

The impairment of pulmonary function is related to the development of pulmonary hypertension in patients with cystic fibrosis?

The impairment of pulmonary function is related to the development of pulmonary hypertension in patients with cystic fibrosis?

AB0630 Gout and hypertension. role of hyperuricemia in the development of hypertension.

BackgroundThe most of patients with gout have various associated diseases, from which hypertension (HTN) has an important prognostic value. The role of hyperuricemia (HUE) in the development of HTN remains...

Analysis of Recent Papers in Hypertension

Analysis of Recent Papers in Hypertension

CLINICAL IMPLICATION OF FATTY ACID CHANGES IN PATIENTS WITH PRIMARY GOUT ASSOCIATED WITH ARTERIAL HYPERTENSION

Aim. To study blood levels of non-esterified fatty acids (NEFAs) and adenyl nucleotides, and fatty acids levels in lipids of erythrocyte membranes in patients with primary gout associated with arterial hypertension (HT). Material and methods. 175 male patients with primary gout were included in the study. According to 24-hour blood pressure (BP) monitoring results patients were split into two groups: 74 patients with normal BP (group 1) and 101 patients with HT (group 2). 29 healthy age-comparable subjects were included into control group. Uric acid, total NEFAs and glycerol blood levels were studied in all patients. Adenyl nucleotides (ATP , ADP and AMP) levels were determined in erythrocytes. Higher fatty acid levels were specified in lipids of erythrocyte membranes, including the following acids: myristinic (С14:0), palmitinic (С16:0), stearic (С18:0), pentadecanic (С15:0), heptadecanic (С17:0), pentadecenic (С15:1), heptadecenic (С17:1), palmitooleic (С16:1), oleic (С18:1), linoleic (С18:2ω6), α-linolenic (С18:3ω3), γ-linolenic (С18:3ω6), dihomo-γ-linolenic (С20:3ω6), arachidonic (С20:4ω6), eicosapentaenoic (С20:5ω3), and docosapentaenoic (С22:5ω3). Results and discussion. Hypertensive patients with gout demonstrated higher NEFAs blood level and greater changes in ATP-ADP-AMP system than normotensive gout patients and healthy subjects as well as 2.2 and 3.7 times higher NEFAs/ATP ratio, respectively. In hypertensive patients with primary gout the composition of fatty acids in erythrocyte membranes lipids changed due to increase in saturated fatty acids amount and decrease in unsaturated fatty acids amount, at that monoenic acid levels increased while polyenic acid levels decreased in unsaturated acids composition. Hypertensive patients with gout shown 1.3 and 2.5 times less levels of ω-3 poly-unsaturated fatty acids (PUFA) than normotensive gout patients and healthy subjects, respectively. At the same time ω-6 PUFA levels changed in bidirectional manner: γ-linolenic and dihomo-γ-linolenic acids levels rose, while arachidonic acid amount was 1.2 and 2.3 times less in comparison with these in gout patients with normal BP and healthy subjects. Conclusion. Study data demonstrate that fatty acid metabolic disturbances possibly contribute to HT development in patients with primary gout.

CLINICAL IMPLICATION OF FATTY ACID CHANGES IN PATIENTS WITH PRIMARY GOUT ASSOCIATED WITH ARTERIAL HYPERTENSION

Aim. To study blood levels of non-esterified fatty acids (NEFAs) and adenyl nucleotides, and fatty acids levels in lipids of erythrocyte membranes in patients with primary gout associated with arterial hypertension (HT). Material and methods. 175 male patients with primary gout were included in the study. According to 24-hour blood pressure (BP) monitoring results patients were split into two groups: 74 patients with normal BP (group 1) and 101 patients with HT (group 2). 29 healthy age-comparable subjects were included into control group. Uric acid, total NEFAs and glycerol blood levels were studied in all patients. Adenyl nucleotides (ATP , ADP and AMP) levels were determined in erythrocytes. Higher fatty acid levels were specified in lipids of erythrocyte membranes, including the following acids: myristinic (С14:0), palmitinic (С16:0), stearic (С18:0), pentadecanic (С15:0), heptadecanic (С17:0), pentadecenic (С15:1), heptadecenic (С17:1), palmitooleic (С16:1), oleic (С18:1), linoleic (С18:2ω6), α-linolenic (С18:3ω3), γ-linolenic (С18:3ω6), dihomo-γ-linolenic (С20:3ω6), arachidonic (С20:4ω6), eicosapentaenoic (С20:5ω3), and docosapentaenoic (С22:5ω3). Results and discussion. Hypertensive patients with gout demonstrated higher NEFAs blood level and greater changes in ATP-ADP-AMP system than normotensive gout patients and healthy subjects as well as 2.2 and 3.7 times higher NEFAs/ATP ratio, respectively. In hypertensive patients with primary gout the composition of fatty acids in erythrocyte membranes lipids changed due to increase in saturated fatty acids amount and decrease in unsaturated fatty acids amount, at that monoenic acid levels increased while polyenic acid levels decreased in unsaturated acids composition. Hypertensive patients with gout shown 1.3 and 2.5 times less levels of ω-3 poly-unsaturated fatty acids (PUFA) than normotensive gout patients and healthy subjects, respectively. At the same time ω-6 PUFA levels changed in bidirectional manner: γ-linolenic and dihomo-γ-linolenic acids levels rose, while arachidonic acid amount was 1.2 and 2.3 times less in comparison with these in gout patients with normal BP and healthy subjects. Conclusion. Study data demonstrate that fatty acid metabolic disturbances possibly contribute to HT development in patients with primary gout.

Single-nucleotide polymorphisms (SNPs) in the endothelial nitric oxide synthase (NOS3) and vascular endothelial growth factor (VEGF) and its relationship to sunitinib-induced hypertension.

4611 Background: Hypertension is a common side-effect in patients treated with sunitinib and is likely associated with inhibition of the VEGF/VEGF receptor(R)-2 pathway. SNPs in VEGF-A, VEGFR-2, but also in NOS3and endothelin-1 (EDN1) have been mentioned as possible candidates associated with a higher risk on development of hypertension. METHODS: A retrospective multicenter study was performed in 255 patients with advanced renal cell cancer and gastrointestinal stromal tumor treated with sunitinib 50 mg/day in a 4 weeks on 2 weeks off or 37.5 mg/day continuous schedule. Office systolic (SBP) and diastolic blood pressure (DBP) were measured at baseline and on days 14 and 28 of the first treatment cycle. Hypertension was graded according to the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE). Seven SNPs in genes encoding for VEGF-A (rs2010963, rs833061, rs3025039, rs699947), VEGFR-2 (rs1870377), EDN1 (rs5370) and NOS3 (rs2070744) were selected. SNPs were univariately tested against hypertension grades according to CTCAE. RESULTS: During the first treatment cycle, sunitinib induced a mean increase of 13 ± 23 mmHg and 10 ± 12 mmHg in SBP and DBP (t-test, P < 0.001), respectively. According to CTCAE, 36.5 % of patients developed hypertension. Among these patients, 10.6%, 12.9% and 12.9% had hypertension grade 1, 2, and 3, respectively. Development of grade 3 hypertension was associated with two copies of the C-allele in VEGF-A (rs833061; Chi-square, P = 0.048), two copies of the A-allele in VEGF-A(rs699947; P = 0.053) and a C-allele in NOS3 (rs2070744; P = 0.051). CONCLUSIONS: SNPs in genes of NOS3 and VEGF-A are associated with the development of severe hypertension in patients treated with sunitinib. In particular, the association between the NOS3 pathway and hypertension induced by an inhibitor of the VEGF/VEGFR-2 pathway is a new finding. Hence, SNPs in VEGF-A and NOS3 genes may identify patients predisposed to develop hypertension on sunitinib treatment.

Anxiety Disorders, Hypertension, and Cardiovascular Risk: A Review

Hypertension, coronary heart disease (CHD), and anxiety disorders all cause substantial morbidity to patients and costs to the healthcare system. Associations between these diseases have been hypothesized and studied for decades. In particular, psychosocial stressors associated with anxiety disorders raise autonomic arousal via the hypothalamic-pituitary axis which increases circulating catecholamines. This heightened arousal is associated with an increased risk of hypertension and a pro-inflammatory state and, consequently, development of coronary heart disease. This association holds across the spectrum of anxiety disorders (generalized anxiety, posttraumatic stress disorder, panic disorder, and obsessive compulsive disorder) and also when controlling for comorbid conditions such as depression and physical ailments. Multiple cross sectional studies reveal a positive association between anxiety and hypertension. These associations are bidirectional, with those with hypertension being more likely to have anxiety and those with anxiety being more likely to have hypertension. However, a few studies have shown no association. Longitudinal studies point to an increased risk of development of hypertension in patients who suffer from anxiety. More convincing studies show links between anxiety symptoms and disorders, including panic disorder and PTSD, and cardiovascular outcomes. Drawing broad conclusions from these studies is challenging, however, given the multiplicity of scales used to measure anxiety disorders. Anxiety, hypertension, and CHD are common conditions seen in primary care, and anxiety may be an important predictor of future CHD outcomes. Better recognition of the association of these conditions and the possible roles of each in development of the other should alert primary care providers to be vigilant in monitoring and treating anxiety, hypertension, and CHD.

Pulmonary hypertension related to pulmonary diseases or hypoxia and its treatment

Pulmonary hypertension often complicates the course of patients with advanced lung disease, and it is associated with a worse prognosis. In the recent classification of pulmonary hypertensive disorders, pulmonary hypertension due to lung disease is considered as a separate category within a group of disorders that were previously referred to as "secondary". The incidence and clinical course of pulmonary hypertension associated with chronic obstructive pulmonary disease is best known among the pulmonary hypertension associated with lung diseases. The pathophysiology and treatment of pulmonary hypertension seen in the course of advanced lung diseases are generally distinct from those of pulmonary arterial hypertension. Chronic hypoxia is the major mechanism implicated for the development of pulmonary hypertension in patients with lung diseases. This article focuses on the recent advances in our knowledge about the pulmonary hypertension due to lung diseases or hypoxia.

A clinical and biological profile to predict risk of development of hypertension in patients with non-clear cell renal cell carcinoma treated with sunitinib.

4601 Background: Hypertension (HTN) due to sunitinib is a common toxicity that has been linked to the development of severe adverse cardiovascular events. Intriguingly, recent observations also suggest a correlation between treatment related HTN and treatment response to anti-angiogenic therapies, including sunitinib. Risk predictors for the development of HTN have not been established. Methods: This is a single-arm phase II trial with a two-stage design to evaluate sunitinib (50 mg daily, 4/2 schedule) in non clear cell RCC (nccRCC). Eligibility criteria included PS 0-2, measurable disease, and a maximum of 2 prior regimens. Monitoring of cardiovascular events included coronary artery disease (CAD) risk-factor assessment and prospective monitoring of blood pressure and cardiac function. In addition, a panel of circulating angiogenic factors was measured prior to therapy and after the first cycle of therapy. Results: 46 pts (65% male, 26% >65 years of age) received an average of 2.6 cycles of sunitinib therapy for nccRCC from March 2007 to December 2009. There were 28 deaths (61%) which were due to progression of disease. 33% of pts developed Grade 2 or higher treatment-related HTN. 0/12 patients without established risk factors for CAD developed treatment related HTN, while 74% (13/17) of pts with two or more CAD risk factors developed treatment-related hypertension. Treatment with sunitinib was associated with a marked reduction in circulating VEGFR-2 levels after one cycle of treatment (p < 1 × 10-10). Intriguingly, baseline levels of soluble VGEFR-2 were two-fold lower in pts who developed treatment-related HTN (p < 0.05). An association between objective response rate and the development of HTN is being explored. Conclusions: HTN associated with sunitinib was observed at a much higher frequency in patients with underlying CAD risk factors. Soluble VEGFR-2 was significantly reduced after treatment in all patients, and was reduced at baseline in pts who developed treatment related HTN. Our observations suggest a complex and potentially important biological interaction between the host vasculature, tumor, and response to sunitinib therapy. No significant financial relationships to disclose.

A Case of Systemic Lupus Erythematosus Presenting as Malignant Hypertension with Hypertensive Retinopathy

The variability of cardiovascular abnormalities is one of the characteristics of systemic lupus erythematosus (SLE). Among the cardiovascular manifestations, hypertension is reported in 14% to 58.1% of patients in diverse ethnic populations, and remains a clinically important issue due to its close relationship with early mortality in patients with SLE. The development of hypertension in patients with SLE has been associated with advanced lupus-related renal disease and the medications used for the treatment of lupus. Malignant hypertension is a serious complication of hypertension; it rarely occurs in patients with SLE. However, it can occur in patients with other complicated medical conditions such as the antiphospholipid antibody syndrome (APS) or cardiac tamponade. Here, we report the case of a patient with SLE and malignant hypertension with hypertensive retinopathy that initially presented without clinical evidence of APS or hypertensive nephropathy.

Relationship between renal size and blood pressure profile in patients with autosomal dominant polycystic kidney disease without renal failure

Enlargement of renal size plays an important role in the development of hypertension in patients with autosomic dominant polycystic kidney disease (ADPKD) and normal renal function. A 24h blood pressure monitoring (ABPM) and a renal echography have been performed in 37 patients with ADPKD and estimated glomerular filtration rate > 60 ml/min/1.73 m(2) to study the relationship between renal size and an altered blood pressure profile in prehypertension stages. 13 patients had normal blood pressure, 11 were diagnosed of masked hypertension, 4 had white coat hypertension and 9 had hypertension. We have found in the normotensive group with a dipper blood pressure profile a positive and statistically significant relationship between renal size and diastolic blood pressure variability. ABPM helps to make an early diagnosis of hypertension and to identify those patients with masked hypertension. This study suggests a relationship between renal size and a blood pressure profile linked to a major cardiovascular risk in normotensive patients with ADPKD.

Abstract 2474: Rho-Kinase Inhibition Improves Endothelium-Dependent Vasodilation during Hyperinsulinemia in Patients with Metabolic Syndrome

Impaired insulin-mediated vasodilation in the skeletal muscle may be involved in the development of hypertension in patients with metabolic syndrome (MetS) and contribute to insulin resistance by diminishing the glucose uptake. Rho-kinase, an effector of the small G protein Rho A, plays an important role in hypertension and is reported to interfere with insulin signaling through serine phosphorylation of insulin receptor substrate-1 in blood vessels. We therefore examined the role of Rho-kinase in the pathophysiology of impaired vascular reactivity in patients with MetS by evaluating the effect of Rho-kinase inhibition on NO-dependent vasodilation during hyperinsulinemia. Forearm blood flow (FBF) responses to acetylcholine (ACh), a stimulus for endothelial release of NO, and sodium nitroprusside (SNP), an exogenous NO donor, were assessed during insulin administration (0.1 mU/Kg/min) using the forearm perfusion technique in patients with MetS (n=10) and matched controls (n=10). Patients with MetS were then randomized to intra-arterial infusion of either fasudil (inhibitor of Rho-kinase, 200 μg/min) or placebo and reactivity to ACh and SNP was reassessed. During hyperinsulinemia, vasodilator responses to both ACh and SNP were blunted in patients with MetS (both P&gt;0.001 vs. controls). In patients who received fasudil, its administration did not change unstimulated FBF (P=0.75 vs. insulin alone); the vasodilator response to ACh, however, was significantly enhanced by fasudil (P=0.009 vs. insulin alone), while the response to SNP was not significantly changed (P=0.56). In patients with MetS who received placebo, vascular reactivity to both ACh and SNP was not different than before (both P&gt;0.05). In conclusion, Rho-kinase inhibition during hyperinsulinemia improves endothelium-dependent vasodilator responsiveness in patients with MetS. This suggests that, under those conditions, intravascular activation of Rho-kinase is involved in the pathophysiology of endothelial dysfunction and may constitute a critical mediator linking metabolic and hemodynamic abnormalities in insulin resistance. As a consequence, targeting Rho-kinase might beneficially impact both vascular function and insulin sensitivity in patients with MetS.

Dynamic time-varying analysis of heart rate and blood pressure variability in cats exposed to short-term chronic intermittent hypoxia

Chronic intermittent hypoxia (CIH) contributes to the development of hypertension in patients with obstructive sleep apnea and animal models. However, the early cardiovascular changes that precede CIH-induced hypertension are not completely understood. Nevertheless, it has been proposed that one of the possible contributing mechanisms to CIH-induced hypertension is a potentiation of carotid body (CB) hypoxic chemoreflexes. Therefore, we studied the dynamic responses of heart rate, blood pressure, and their variabilities during acute exposure to different levels of hypoxia after CIH short-term preconditioning (4 days) in cats. In addition, we measured baroreflex sensitivity (BRS) on the control of heart rate by noninvasive techniques. To assess the relationships among these indexes and CB chemoreflexes, we also recorded CB chemosensory discharges. Our data show that short-term CIH reduced BRS, potentiated the increase in heart rate induced by acute hypoxia, and was associated with a dynamic shift of heart rate variability (HRV) spectral indexes toward the low-frequency band. In addition, we found a striking linear correlation (r = 0.97) between the low-to-high frequency ratio of HRV and baseline. CB chemosensory discharges in the CIH-treated cats. Thus, our results suggest that cyclic hypoxic stimulation of the CB by short-term CIH induces subtle but clear selective alterations of HRV and BRS in normotensive cats.