Development Of Sustained Hypertension Research Articles

The influence of oxidative stress on cardiac remodeling in obese adolescents

Oxidative stress seems to be an important link between obesity and cardiovascular disease. The aim of our study was to assess oxidative stress in obese patients stratified according to ambulatory blood pressure status and to determine independent predictors of abnormal left ventricular geometry.A cross-sectional study was conducted. A total of 113 obese participants referred for 24-h ambulatory blood pressure monitoring (ABPM) aged 9–19 years, and 29 healthy controls were enrolled. In addition to anthropometric and biochemical measurements, such as fasting serum levels of glucose, insulin, lipid profile, and oxidative biomarkers, ABPM and echocardiography were performed.According to ABPM results, obese subjects were split in two groups: 57 hypertensive and 56 normotensive. Both hypertensive and normotensive obese participants had higher levels of oxidative stress parameters (pro-oxidative/antioxidative balance and total oxidant status) compared with control group. Levels of superoxide anion (O2−) and sulfhydryl groups were higher in obese hypertensive participants as compared to obese normotensive and control groups. Abnormal left ventricular geometry among obese participants was independently associated with O2− (p = .006) and body mass index z score (p = .020), with no significant impact of gender, while age and systolic blood pressure exhibited interaction term for the outcome.The independent effect of oxidative mechanisms on left ventricular geometry appears to start in childhood. Oxidative stress occurs in obese adolescents prior to the development of sustained hypertension.

Risk factors for arterial hypertension after liver transplantation

Arterial hypertension represents a common complication of immunosuppressive therapy after liver transplantation (LT). The aim of the study is to evaluate the prevalence and risk factors associated with hypertension after LT. From a cohort of 323 cirrhotic patients who underwent LT from 2008 to 2012, 270 patients were retrospectively evaluated, whereas 53 (16.4%) patients deceased. Hypertension was defined as blood pressure ≥140/90 mm Hg in at least two visits and/or the need for antihypertensive therapy. The prevalence of hypertension was 15% before LT and significantly increased up to 53% after LT (P < .001). Mean follow-up was 43 ± 19 months. In normotensive (NT) subjects at baseline, 35.9% developed sustained hypertension after LT, whereas 15.2% developed transient hypertension within the first month after LT, and then returned NT. The development of sustained hypertension after LT was related to the mammalian target of rapamycin inhibitor treatment (odds ratio [OR], 4.02; 95% confidence interval [CI], 1.26–13.48; P = .02), alcoholic cirrhosis before LT (OR, 3.38; 95% CI, 1.44–8.09; P = .005), and new-onset hepatic steatosis after LT (OR, 2.13; 95% CI, 1.10–4.11; P = .02). Tacrolimus, the etiology and severity of liver disease, and other immunosuppressive regimens were not related to the development of hypertension after LT. In our cohort, the prevalence of arterial hypertension has increased up to 53% after LT, and metabolic comorbidities and immunosuppressive treatment with mammalian target of rapamycin inhibitors are the risk factors for the development of hypertension after LT.

Expression of catechol-O-methyltransferase (Comt), mineralocorticoid receptor (Mlr), and epithelial sodium channel (ENaC) genes in kidneys of hypertensive ISIAH rats at rest and during response to stress

Emotional stress plays a significant role in the processes of the development of arterial hypertension, especially in the presence of genetic predisposition. The origin and maintenance of hypertensive status during stress development can be activated by the sympathetic nervous system. An increase in sympathetic stimulation can, in turn, result in a change in the functions of kidneys, which provide fluid and electrolyte balance of the organism. A comparative study of the mRNA expression level of catechol-o-methyltransferase (Comt), mineralocorticoid receptor (Mlr), and β-subunit of epithelial sodium channel (β-ENaC) genes was conducted on the kidneys of hypertensive ISIAH rats and normotensive WAG rats at rest and after the effect of emotional stress. The discovered changes in the expression level of the selected genes confirm their involvement in increased sympathetic stimulation of the kidney, along with changes in the function of kidney regulation of fluid and electrolyte balance, which is an important factor of the development of sustained hypertension in the ISIAH rats strain.

Longitudinal tracking of muscle sympathetic nerve activity and its relationship with blood pressure in subjects with prehypertension

Prehypertension is associated with increased cardiovascular events. While the “tracking phenomenon” is an important longitudinal characteristic of blood pressure (BP), changes in muscle sympathetic nerve activity (MSNA) over time remain unclear. This study tested the hypothesis that MSNA tracking contributes to BP trends in prehypertension. BP and MSNA were assessed in 13 prehypertensive males at rest, during hand grip and mental stressors at baseline and after 8 years. Baseline office BP averaged 127 ± 2/81 ± 2 mmHg and MSNA 24 ± 4 bursts/min. BP increased by 7 ± 2/5 ± 2 mmHg (P < 0.01) and MSNA by 11 ± 2 bursts/min (P < 0.001) at follow-up. SBP and DBP were interrelated at baseline (r = 0.65, P = 0.02) and at follow-up (r = 0.78, P = 0.002). MSNA tracking (r = 0.82; P < 0.001) was similar to BP. MSNA was strongly related to DBP at baseline (r = 0.73; P < 0.01) and follow-up (r = 0.64; P = 0.01), more so than SBP. BMI increased (P < 0.001) at follow-up but was unrelated to BP or MSNA. Despite comparable pressor and cardiac increases to handgrip and mental stressors, sympathetic responses were blunted, more pronounced to isometric test (P < 0.006) at follow-up. In conclusion, the trend in MSNA corresponds with BP changes over time suggesting that tonic sympathetic activation may contribute to time-related increase in resting BP and the development of sustained hypertension in prehypertension.

Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 6: Hypertension: A Scientific Statement from the American Heart Association and the American College of Cardiology.

An elevation of blood pressure (BP) in the systemic circulation (hypertension) is the most common cardiovascular condition in the general population and considered to be the most ubiquitous cardiovascular risk factor in competitive athletes. Competitive athletes include those athletes involved in organized sports that typically occur in schools, communities, and professional leagues, including but not limited to intramural and league sports in which medical supervision is typically required. Although most competitive athletes are between the ages of 20 and 40 years, many younger people now participate in competitive athletics. The 2013 update from the American Heart Association using the National Health and Nutrition Examination (NHANES) data from 2007 to 2010 estimates that 9.1% of men aged 20 to 34 years and 6.7% of women of that age are hypertensive, based on having an elevated BP measurement or answering “yes” to the question, “Are you taking antihypertensive medication or were you told that you had hypertension?”1 The prevalence in children and adolescents is estimated to be ≈3.5%, with higher percentages in older and obese children.2 The diagnosis of hypertension is based on the subject having an elevated BP at or above certain levels measured by routine sphygmomanometry under appropriate conditions on at least 2 separate occasions separated by at least 1 week.3 However, BP measurements in the competitive athlete are typically obtained by different healthcare providers, which makes it particularly necessary that the testing conditions be standardized before the diagnosis of hypertension is made. People >18 years of age with a BP >140 mm Hg systolic and/or >90 mm Hg diastolic are considered to have hypertension.3 In children and adolescents, hypertension is defined as average systolic or diastolic BP levels greater than the 95th percentile for sex, age, and height; however, earlier physical maturation of the competitive athlete leaves …

Arterial Baroreceptor Reflex Counteracts Long-Term Blood Pressure Increase in the Rat Model of Renovascular Hypertension

IntroductionThe present study tested the hypothesis that long-term effects of baroreceptor activation might contribute to the prevention of persistent arterial blood pressure (BP) increase in the rat model of renovascular hypertension (HTN).MethodsRepetitive arterial baroreflex (BR) testing was performed in normo- and hypertensive rats. The relationship between initial arterial BR sensitivity and severity of subsequently induced two-kidney one-clip (2K1C) renovascular HTN was studied in Wistar rats. Additionally, the time course of changes in systolic BP (SBP) and cardiac beat-to-beat (RR) interval was studied for 8 weeks after the induction of 2K1C renovascular HTN in the rats with and without sinoaortic denervation (SAD). In a separate experimental series, cervical sympathetic nerve activity (cSNA) was assessed in controls, 2K1C rats, WKY rats, and SHR.ResultsThe inverse correlation between arterial BR sensitivity and BP was observed in the hypertensive rats during repetitive arterial BR testing. The animals with greater initial arterial BR sensitivity developed lower BP values after renal artery clipping than those with lower initial arterial BR sensitivity. BP elevation during the first 8 weeks of renal artery clipping in 2K1C rats was associated with decreased sensitivity of arterial BR. Although SAD itself resulted only in greater BP variability but not in persistent BP rise, the subsequent renal artery clipping invariably resulted in the development of sustained HTN. The time to onset of HTN was found to be shorter in the rats with SAD than in those with intact baroreceptors. cSNA was significantly greater in the 2K1C rats than in controls.ConclusionsArterial BR appears to be an important mechanism of long-term regulation of BP, and is believed to be involved in the prevention of BP rise in the rat model of renovascular HTN.

Sexual Dimorphism in the Transition From Masked to Sustained Hypertension in Healthy Youths

The risk and factors related to the development of hypertension among healthy youths with elevated ambulatory and normal conventional blood pressure, masked hypertension, have not been established. We performed a long-term follow-up study assessing how hypertension develops over time in healthy, masked hypertensive youths. The potential sex dimorphism in the incidence and timing of the development of hypertension has been analyzed. In a long-term follow-up study (median follow-up, 36 months), we enrolled 272 healthy conventional normotensive youths (aged 6-18 years; 55.8% girls) of whom 39 had masked hypertension at baseline. Development of sustained hypertension (hypertension in both conventional and ambulatory measurement) was recorded. The daytime systolic blood pressure increased from baseline to last available follow-up in boys (3.5 mm Hg; P<0.001) but not in girls (0.7 mm Hg; P=0.23), leading to a significant between-sex difference (P=0.0022). The incidence of sustained hypertension was 7.0/100 subjects/y (n=12) in masked hypertensives and 0.6/100 subjects/y (n=4) in normotensives. Masked hypertensive boys more frequently proceeded to sustained hypertension as compared with masked hypertensive girls (50.0% versus 17.4%; P=0.041). Masked hypertension at baseline (hazard ratio, 15.6; 95% confidence interval, 4.91-49.7; P<0.0001) and male sex (hazard ratio, 3.25; 95% confidence interval, 1.12-9.39; P=0.0295) were independent factors associated with the incidence of sustained hypertension during the follow-up. In youth, masked hypertension is a precursor of sustained hypertension. The risk of developing sustained hypertension is higher in boys than it is for girls. The fact that masked hypertension is not prognostically innocent increases the importance of the diagnosis at an early age.

Abstract 384: Association of Insulin Resistance With Ambulatory Blood Pressure in Normotensive and Prehypertensive Patients

Introduction Hypertension and insulin resistance are well established risk factors for atherosclerosis. Accumulated evidence also suggests that insulin resistance plays a contributory role in the development of essential hypertension. Previous studies have focused on patients with established hypertension, using clinic blood pressure (BP) measurements. Ambulatory Blood Pressure Monitoring (ABPM) records BP at 20-30 minute intervals over 24 hours, providing an average BP exposure over time. We tested the hypothesis that insulin resistance and blood pressure are associated in normotensive and prehypertensive patients, using ABPM to quantify average BP. Methods Data were collected for 140 subjects (87 female, 53 male; 117 non-black, 23 black). In addition to clinic BP, ABPM was used to obtain average SBP and DBP over 24 hours. Insulin resistance (IR) was quantified using the QUantitative Insulin sensitivity ChecK Index (QUICKI), calculated from fasting glucose and insulin levels with the formula QUICKI = 1/(log [Fasting insulin in mU/l] + log [Fasting plasma glucose in mg/dl]). Multiple linear regression was used to assess IR as a predictor of ABPM-derived BP measures, controlling for BMI, gender, age, and race. Results In the entire cohort using ABPM, there was a significant association of IR with DBP24 (p=0.012) but not SBP24 (p=0.11). The association between IR and clinic SBP was marginally significant (p=0.09); DBP NS (p=0.33). After stratifying by gender, IR was significantly associated with SBP24, Daytime SBP (p=0.064, 0.044), DBP24 and Daytime DBP (p=0.02 and p=0.015) in males; no association was found in females. Conclusions This study demonstrates a significant association of IR with average 24-hour DBP in males and females combined. Stratified by gender, our finding using ABPM of a significant association of IR with SBP in males but not in females supports previous findings using clinic BP in the NHANES cohort. In conclusion, these data demonstrate the presence of IR in prehypertension, and lend support to the theory that IR may contribute to later development of sustained hypertension, particularly in males. Additionally, our study highlights the importance of further research using ABPM for a more precise estimate of average BP level.

Irreversible Renal Damage after Transient Renin-Angiotensin System Stimulation: Involvement of an AT1-Receptor Mediated Immune Response

Transient activation of the renin-angiotensin system (RAS) induces irreversible renal damage causing sustained elevation in blood pressure (BP) in Cyp1a1-Ren2 transgenic rats. In our current study we hypothesized that activation of the AT1-receptor (AT1R) leads to a T-cell response causing irreversible impairment of renal function and hypertension. Cyp1a1-Ren2 rats harbor a construct for activation of the RAS by indole-3-carbinol (I3C). Rats were fed a I3C diet between 4–8 weeks of age to induce hypertension. Next, I3C was withdrawn and rats were followed-up for another 12 weeks. Additional groups received losartan (20 mg/kg/day) or hydralazine (100 mg/kg/day) treatment between 4–8 weeks. Rats were placed for 24h in metabolic cages before determining BP at week 8, 12 and 20. At these ages, subsets of animals were sacrificed and the presence of kidney T-cell subpopulations was investigated by immunohistochemistry and molecular marker analysis. The development of sustained hypertension was completely prevented by losartan, whereas hydralazine only caused a partial decrease in BP. Markers of renal damage: KIM-1 and osteopontin were highly expressed in urine and kidney samples of I3C-treated rats, even until 20 weeks of age. Additionally, renal expression of regulatory-T cells (Tregs) was highly increased in I3C-treated rats, whereas the expression of T-helper 1 (Th1) cells demonstrated a strong decrease. Losartan prevented these effects completely, whereas hydralazine was unable to affect these changes. In young Cyp1a1-Ren2 rats AT1R activation leads to induction of an immune response, causing a shift from Th1-cells to Tregs, contributing to the development of irreversible renal damage and hypertension.

Abstract 354: Mitochondrial Hyper-function in Renal Proximal Tubule Cells from Young Spontaneously Hypertensive Rats

Recent evidence suggests that mitochondria play roles in the pathogenesis of hypertension. However, it is not clear whether mitochondrial dysfunction precedes or follows the development of hypertension. We hypothesize that mitochondrial bioenergetics is altered in renal proximal tubule (RPT) cells from spontaneously hypertensive rats (SHRs) and this alteration may occur prior to the development of sustained hypertension. Using immortalized RPT cells from 4-8 week old normotensive Wistar-Kyoto (WKY) and SHRs, we measured oxygen consumption rate (OCR) and compared the parameters of cellular bioenergetic in these RPT cells. Basal OCR was significantly higher in RPT cells from SHRs than WKY rats (245.5±31.9 vs. 154.4±43.7 pmol/min per 20,000 cells, mean±SD, P&lt;0.001);the ATP synthesis-coupled OCR (65.9±3.3% vs. 55.0±6.6%, of basal OCR, P&lt;0.001), maximum respiration (609.0±120.4 vs. 215.7±65.5 pmol/min per 20,000 cells, P&lt;0.001) and reserve respiration (147.8±39.0% vs, 40.0±15.4% of basal OCR P&lt;0.001) were also significantly higher in RPT cells from SHRs than WKY rats. In contrast, proton leak-linked OCR (15.4±3.6% vs. 19.2±5.9% of basal OCR, P&lt;0.05) was lower in RPT cells from SHRs than WKY rats, and non-mitochondrial OCRs were similar (45.2±7.0 vs. 41.3±19.8 pmol/min per 20,000 cells, P&gt;0.05). In support of these observations, adenosine triphosphate (ATP) levels were significantly higher in RPT cells from SHRs than WKY rats. Taken together, the observed bioenergetic alterations may contribute to the early mitochondrial dysfunction in RPT cells from SHRs prior to the onset of sustained hypertension.

Association between coffee consumption and risk of hypertension

Background. The longitudinal relationship between coffee use and hypertension is not well known.Aim. We did a prospective study to investigate if there is a temporal relationship between coffee consumption and development of sustained hypertension.Method. We assessed 1107 white subjects with elevated blood pressure who were followed up for 6.4 years. Coffee intake and other life‐style factors were ascertained from regularly administered questionnaires. Incident physician‐diagnosed hypertension was the outcome measure.Results. During the follow‐up, 561 subjects developed sustained hypertension, whereas 546 subjects did not meet the criteria for treatment. Coffee drinkers developed sustained hypertension more frequently than abstainers (53.1% versus 43.9%, P = 0.007). The incidence of hypertension did not differ between moderate and heavy coffee drinkers. Kaplan‐Meier analysis confirmed that sustained hypertension was developed more frequently by coffee drinkers compared with nondrinkers (P<0.001). The adjusted relative risk of hypertension was greater in both categories of coffee drinking than in abstainers (hazard ratio, 95% confidence limit (CL) = 1.24, 1.06–1.44). The risk of hypertension associated with coffee drinking increased gradually with increasing level of alcohol use (adjusted P for interaction = 0.005).Conclusions. In subjects screened for stage 1 hypertension a nonlinear association was found between coffee consumption and development of sustained hypertension.

Functional allelic heterogeneity and pleiotropy of a repeat polymorphism in tyrosine hydroxylase: Prediction of catecholamines and response to stress in twins

Tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, has a common repeat polymorphism, (TCAT)n. We asked whether variation at TH influenced the autonomic stress responses in a human twin study design. Autonomic traits displayed substantial heritability (h2), up to h2=56.8±7.5% (p<0.0001) for norepinephrine secretion, and h2=61±6% (p<0.001) for heart rate. Common (TCAT)n alleles, particularly (TCAT)6 and (TCAT)10i, influenced such traits (including catecholamine secretion, as well as basal and post-stress heart rate) in allele copy number dose-dependent fashion, though in directionally opposite ways, indicating functional allelic heterogeneity. Multivariate ANOVA documented genetic pleiotropy: joint effects of the (TCAT)10i allele to influence both biochemical (norepinephrine) and physiological (heart rate) traits. (TCAT)6 allele frequencies were lower in normotensive twins at genetic risk of hypertension, consistent with an effect to protect against later development of hypertension, and suggesting that the traits predicted by these variants in still-normotensive subjects are early, heritable, “intermediate phenotypes” in the pathogenetic scheme for later development of sustained hypertension. We conclude that common allelic variation within the TH locus exerts a heritable effect on autonomic control of the circulation, and that such variation may have implications in later development of cardiovascular disease. Clinical Pharmacology & Therapeutics (2005) 77, P6–P6; doi: 10.1016/j.clpt.2004.11.025

Functional allelic heterogeneity and pleiotropy of a repeat polymorphism in tyrosine hydroxylase: prediction of catecholamines and response to stress in twins.

Tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, has a common tetranucleotide repeat polymorphism, (TCAT)(n). We asked whether variation at (TCAT)(n) may influence the autonomic nervous system and its response to environmental stress. To understand the role of heredity in such traits, we turned to a human twin study design. Both biochemical and physiological autonomic traits displayed substantial heritability (h(2)), up to h(2) = 56.8 +/- 7.5% (P < 0.0001) for norepinephrine secretion, and h(2) = 61 +/- 6% (P < 0.001) for heart rate. Common (TCAT)(n) alleles, particularly (TCAT)(6) and (TCAT)(10i), predicted such traits (including catecholamine secretion, as well as basal and poststress heart rate) in allele copy number dose-dependent fashion, although in directionally opposite ways, indicating functional allelic heterogeneity. (TCAT)(n) diploid genotypes (e.g., [TCAT](6)/[TCAT](10i)) predicted the same physiological traits but with increased explanatory power for trait variation (in contrast to allele copy number). Multivariate ANOVA documented genetic pleiotropy: joint effects of the (TCAT)(10i) allele on both biochemical (norepinephrine) and physiological (heart rate) traits. (TCAT)(6) allele frequencies were lower in normotensive twins at genetic risk of hypertension, consistent with an effect to protect against later development of hypertension, and suggesting that the traits predicted by these variants in still-normotensive subjects are early, heritable, "intermediate phenotypes" in the pathogenetic scheme for later development of sustained hypertension. We conclude that common allelic variation within the tyrosine hydroxylase locus exerts a powerful, heritable effect on autonomic control of the circulation and that such variation may have implications in later development of cardiovascular disease traits such as hypertension.

Epidemiology of Hypertension Based on Ambulatory Blood Pressure Monitoring and Self-Measurement of Blood Pressure at Home

Measurements of ambulatory blood pressure (ABP) and of home blood pressure (HBP) as an adjunct to casual/clinic BP (CBP) measurements are currently widely used for the diagnosis and treatment of hypertension. We have monitored a rural cohort of people from the population of Ohasama, Japan, with respect to their prognosis and have previously reported that ABP and HBP are superior to CBP for the prediction of cardiovascular mortality. We examined the prognostic significance of white-coat hypertension for mortality and found that the relative hazard for the overall mortality of patients with white-coat hypertension was significantly lower than that for true hypertension during 5-year observation period but observed that the development of sustained hypertension was more frequent in patients with white-coat hypertension than those with true normotension during 10-year observation period. Our results also confirmed that day-by-day variability as well as short-term blood pressure variability (as measured every 30 min) was independently associated with cardiovascular mortality. In addition, research has recently focused on isolated systolic hypertension and pulse pressure as independent risk factors for poor cardiovascular prognosis. The Ohasama study also clearly demonstrated that isolated systolic hypertension and increased pulse pressure, as assessed by HBP, were associated with an increase in the risk of cardiovascular mortality. Concerning diurnal blood pressure variation, the relative hazard for cardiovascular mortality increased in non-dippers and inverted dippers while that in extreme dipper did not. The Ohasama study also clearly demonstrated that nocturnal BP levels in hypertensive patients with extreme dipper were significantly higher than those in normotensive subjects. The Ohasama study showed that the level and variability of hypertension as assessed by ABP and HBP are independent predictors of cardiovascular morbidity and mortality. It also demonstrated an independent association between the prognosis of hypertension and each component of ABP and HBP, indicating the prognostic significance of these blood pressure measurements.

654 White coat hypertension and development of sustained hypertension

654 White coat hypertension and development of sustained hypertension

Influence of Plasma Insulin Levels on Antinatriuretic and Vasoconstrictor Actions of Angiotensin‐II

The objective of the present study is to investigate whether plasma insulin levels play a role in the antinatriuretic and vasoconstrictor actions of angiotensin‐II (Ang‐II). We evaluated antinatriuretic function of endogenous Ang‐II using an AT1 receptor antagonist, candesartan in anesthetized Sprague‐Dawley rats. In control rats, candesartan produced significant increases in natriuresis and diuresis and these effects were abolished in streptozocin (STZ, 55 mg/kg i.p.) treated rats. Replacement of insulin restored these renal effects of candesartan. In a separate group of rats pretreated with an autonomic ganglionic blocker, pressor responses to Ang‐II and norepinephrine (NE) before or after L‐NNA, a nitric oxide synthase inhibitor were not affected by STZ treatment. However, insulin replacement greatly augmented these responses. These data provide evidence in vivo showing that insulin can enhance both antinatriuretic and vasoconstrictor actions of Ang‐II. Hence exaggerated renal and vascular effects of Ang‐II in the obese Zucker rats observed in our previous studies may be related to hyperinsulimemia and this phenomena could contribute to salt‐sensitivity and development of sustained hypertension.

Orthostatic hypertension in patients with type 2 diabetes.

The prevalence and clinical importance of orthostatic hypertension (OHT) in diabetic patients has not been elucidated, in contrast to orthostatic hypotension, which is occasionally found in diabetic patients with autonomic neuropathy. The prevalence and severity of orthostatic hypertension was investigated in 277 Japanese male patients with type 2 diabetes, including 90 hypertensive patients and 128 nondiabetic age-matched male subjects. Patients treated with antihypertensive drugs were excluded from the study. OHT was defined as an increase in diastolic blood pressure (DBP) from <90 to >or=90 mmHg and/or an increase in systolic blood pressure (SBP) from <140 to >or=140 mmHg after standing from supine position. Clinical profiles and several serum biochemical parameters were determined in addition to chest X-rays and electrocardiograms. The prevalence of OHT in normotensive and hypertensive diabetic patients was significantly higher than in control subjects (12.8 vs. 1.8%, P < 0.01, for normotensive patients; 12.6 vs. 11.1%, not significant, for hypertensive patients). Orthostasis induced a mean increase of 6.8 +/- 11.4 mmHg in SBP and 9.1 +/- 5.2 mmHg in DBP in diabetic patients with OHT compared with those without OHT (-1.0 +/- 9.0 and 3.8 +/- 6.6 mmHg, respectively). Vibration sensation in the lower limb was reduced in diabetic patients with OHT, but the percent coefficient of variation of RR interval, cardio-to-thoracic ratio on chest X-ray, and serum triglyceride levels were higher in these patients compared with normotensive diabetic patients without OHT. Orthostatic hypertension is a novel complication in normotensive diabetic patients and may associate with early stage neuropathy and development of sustained hypertension.

Circadian systemic haemodynamics in borderline and mild hypertension.

Circadian variations in blood pressure (BP), stroke volume (SV), heart rate (HR), cardiac output (CO) and total peripheral resistance (TPR) were determined by a pulse contour method from the intra-arterial pulse wave in 32 normotensive (NT), 32 borderline hypertensive (BHT) and 31 hypertensive (HT) middle-aged men. Daytime averages were used as the reference levels. The nocturnal decrease in BP and HR were similar in the three groups. In the night, SV did not change in the NT group, but was increased in the BHT and HT groups. The nocturnal increase in SV may reflect reduced venous capacity causing increased cardiac filling. As a consequence of the difference in SV, the nocturnal CO fall was diminished in the HT group as compared with the NT group. Moreover, TPR had a tendency to decrease in the HT group, which may be considered as a baroreflex response to buffer the expected rise in BP. Five years later, 25 NT, 24 BHT and 19 HT subjects were reassessed using casual BP measurements. In the NT and BHT groups, six and 17 subjects, respectively, had progressed to hypertension. In a logistic regression model for those who became HT, the nocturnal increase in SV was a significant predictor for future hypertension. In conclusion, the results suggest that circadian systemic haemodynamics may be altered before BP is markedly elevated, and that haemodynamic studies might be useful in predicting the development of sustained hypertension.

Isolated office hypertension: are there any markers of future blood pressure status?

The introduction of ambulatory blood pressure monitoring into clinical practice has defined a clinical condition called 'isolated office hypertension'. The aim of this study was to evaluate the long-term systolic and diastolic blood pressure changes in patients with isolated office hypertension and to identify the presence of markers capable of identifying which patients will develop sustained hypertension. All the 407 patients enrolled had a random office systolic or/and diastolic blood pressure of over 140/90mmHg and a mean daytime ambulatory blood pressure of 130/84mmHg or less. At enrollment, each patient underwent a 'baseline examination' made up of a physical evaluation, a 24h ambulatory blood pressure monitoring, and a mental arithmetic test performed at the end of the 24h ambulatory monitoring. Of the 173 patients finally studied, 102 (58.9%) developed sustained hypertension with an increase in both ambulatory systolic and diastolic blood pressure. At the time of the baseline examination, the patients were divided into two groups. Group A included patients with mean ambulatory systolic and diastolic blood pressures in the first hour of 130/84mmHg or less; group B included patients with mean ambulatory systolic and diastolic pressures in the first hour of greater than 130/84mmHg. During the mental arithmetic test, the systolic and heart rate values increased significantly only in group B patients. Of the 102 patients who had become hypertensive by the time of the follow-up examination, 84 (82%) belonged to group B. These data suggest that isolated office hypertension may indeed be a transitional state towards the development of sustained hypertension. Moreover, the mean ambulatory blood pressure value during the first hour can be considered to be a marker of a higher risk of developing sustained hypertension.

Salt-sensitive hypertension develops after short-term exposure to Angiotensin II.

We hypothesized that short-term exposure to angiotensin II (Ang II) could result in structural and functional changes in the kidney that would favor sodium retention and the development of sustained hypertension. To test this hypothesis, rats were exposed to pressor doses (435 ng. kg-1. min-1) of Ang II for 2 weeks. The infusion of Ang II was associated with acute hypertension, renal dysfunction, proteinuria, and focal tubulointerstitial and vascular damage. At sites of the tubulointerstitial damage, there was a reduction in peritubular capillary endothelial cell staining. By use of immunostaining, we found focal loss of endothelial nitric oxide synthase (eNOS) in the peritubular capillaries at sites of injury and a generalized reduction in eNOS in collecting ducts, thin loops of Henle, and vascular bundles in the medulla. When the Ang II infusion ended, the rats became normotensive and renal function returned toward normal. However, exposure of the rats to high salt diet (4% NaCl) resulted in the redevelopment of hypertension after 3 to 4 weeks. Rats maintained on a high salt diet with no prior exposure to Ang II and rats placed on low salt diet (0.1% NaCl) after exposure to Ang II remained normotensive. Thus, we report a new model of salt-sensitive hypertension induced by transient exposure to pressor doses of Ang II. The mechanism may relate to microvascular injury with peritubular capillary loss coupled with functional changes, such as a loss in intrarenal nitric oxide formation, that could alter the ability of the kidney to excrete a salt load.