Systolic Blood Pressure Rose Research Articles

Euglycemic Clamp Insulin Sensitivity and Longitudinal Systolic Blood Pressure

Insulin resistance may be an independent risk factor for the development of hypertension, but change in blood pressure (BP) over time has not been adequately studied in healthy individuals fully characterized for insulin sensitivity. In the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study, we measured insulin sensitivity (M/I) using the euglycemic clamp technique in 1073 healthy European adults (587 women, 486 men) aged 30 to 60 years followed up 3 years later. Systolic BP (SBP) at baseline was higher in insulin-resistant women (ie, those in the low sex-specific M/I tertile) compared with those in the intermediate ( P <0.001) or high tertiles ( P =0.06; mean±SD: 117±13, 111±12, 114±12 mm Hg, respectively). It did not differ across M/I tertiles in men. After adjustment for age, body mass index, baseline SBP, and other covariates, low insulin sensitivity (M/I) predicted a longitudinal rise in SBP in women but not in men; M/I was not associated with change in diastolic BP. SBP rose over time in both sexes and within all M/I tertiles ( P <0.05), except in women with high insulin sensitivity. Therefore, in women (but not in men), low insulin sensitivity was associated with higher SBP at 3 years, and high insulin sensitivity was associated with a lower rise in SBP over time.

A FEW HYPERTENSIVE HUMANS RESPOND TO MAGNESIUM SUPPLEMENTS WITH A RISE IN BLOOD PRESSURE, suggesting a genetic subgroup in response to nutritional Mg

Far back as 1942, Winkler showed that i.v. Mg infusion lowered blood pressure (BP) in humans; that study also showed one subject's systolic blood pressure rose upon i.v. Mg infusion. Analysis of 41 clinical studies of Mg supplements on blood pressure show that 20 mmol (486 mg)/day Mg will significantly decrease high blood pressure in humans, with half that dose being effective for subjects on anti‐hypertnesive medications.Few of these 41 studies report individual blood pressure results, but in the 8 that do, all but one show “outliers” for whom magnesium supplements resulted in INCREASED blood pressure during the study. For this almost completely consistent finding (7 of 8 studies), 15 – 52% of 7 studies’ subjects had at least a slight rise in diastolic, systolic or mean blood pressure upon Mg supplementation, while 1 – 17% of studies’ individuals were significant outliers, showing large rises in these blood pressure parameters, [i.e. > 5 mm Hg rise for DBP, > 20 mm Hg rise for SBP or > 10 Hg mm rise for MBP]. Only one of the 8 studies reporting individual subjects’ results showed all subjects with a drop in blood pressure.Combined, these 8 studies show 207 individual results of Mg therapy for blood pressure, of which 6.3 – 7.3% showed a substantial rise in the measured BP parameter, opposite the majority and group statistical results, suggesting variant genetic allele(s) or polymorphism(s) in the human genome for the handling of Mg supplements and how they effect a blood pressure response. Mg supplementation for blood pressure, while therapeutic for the majority of hypertensives, may be contra‐indicated for a small minority beyond the gastro‐intestinal considerations.

A rise in systolic blood pressure during adenosine stress myocardial perfusion imaging does not increase the likelihood of an abnormal scan

Background: The normal physiologic response to vasodilators, such as adenosine, is a fall in systolic blood pressure (SBP). However, in some cases, a patient's SBP rises rather than falls during adenosine stress myocardial perfusion imaging (MPI). It has been anecdotally suggested that this paradoxical response may result from a heightened adrenergic state due to adenosine-induced ischemia. We sought to assess whether ischemia is more common among patients whose SBP rises during adenosine stress MPI. Methods: Scan findings and SBP responses for 866 consecutive patients (age = 65.7±12.6 years; 356 men) undergoing adenosine stress MPI were assessed. Adenosine (140 μg/kg/min) was infused for six minutes (no concomitant exercise). MPI was performed using either a 201Tl stress / redistribution or a dual isotope ( 201Tl rest / 99mTc stress) protocol. Scans were interpreted by experienced readers. Results: A rise in SBP ≥10 mmHg was seen in 61 (7%) patients, while 227 (26%) had a flat response (ΔSBP <10 mmHg) and 578 (67%) had a drop in SBP ≥10 mmHg. The ratio of ischemic to non-ischemic scans in women was the same, irrespective of SBP response. In men there was a trend toward fewer ischemic scans among patients whose SBP rose compared with those whose SBP fell during testing (p = 0.08). Men with a flat SBP response had an intermediate scan ratio. MPI Result SBP Decreased SBP Flat SBP Increased Male Female Male Female Male Female % with any ischemia 42 29 34 25 29 27 % with no ischemia 58 71 66 75 71 73 Conclusion: A rise in SBP during adenosine infusion is not associated with a higher likelihood of ischemia in patients undergoing adenosine stress MPI. In fact, there is a trend toward less ischemia among men who demonstrate such a paradoxical response. It is unlikely that a rise in SBP during adenosine stress MPI is due to an adrenergic surge in response to ischemia. The finding of more ischemia in men with a fall in SBP may help to account for the observation that men with exaggerated SBP responses to adenosine have a higher risk of cardiac death.

Genetic inactivation of the B2 receptor in mice worsens two-kidney, one-clip hypertension: role of NO and the AT2 receptor.

Previous studies have suggested that activation of angiotensin II (ANG II) type 2 (AT2) receptors results in nitric oxide (NO) release via activation of endothelial bradykinin B2 (B2R) receptors. The present study was performed to examine the interplay of AT2 and B2R in the development and maintenance of two-kidney, one-clip (2K1C) Goldblatt hypertension. B2R knockout (B2R-/-) mice and their wild-type controls (B2R+/+) underwent clipping of the right renal artery and were infused with either saline (SAL) or PD 123319, an AT2 receptor antagonist (PD), via an osmotic pump implanted intraperitoneally. Systolic blood pressure (SBP) was measured in conscious mice. On day 27, mean arterial pressure (MAP) responses were measured in response to consecutive blockade of AT(2) receptors and NO synthase (NOS). A significant and sustained rise in SBP was observed in both 2K1C B2R+/+ and B2R-/- versus sham-operated groups from day 10 to day 24 after clipping. After this time, SBP rose to significantly higher levels in 2K1C/B2R-/- than in 2K1C/B2R+/+ mice. MAP on day 27 was also higher in 2K1C/B2R-/- than 2K1C/B2R+/+ mice. Chronic PD infusion did not alter the course of hypertension in 2K1C/B2R+/+ or 2K1C/B2R-/- mice as compared with saline-infused mice. Likewise, acute PD infusion did not affect MAP in any of the groups. However, acute NOS inhibition caused significantly greater increases in MAP in 2K1C/B2R+/+ and PD/2K1C/B2R+/+ than 2K1C/B2R-/- and PD/2K1C/B2R-/- mice. These results indicate that B2R inactivation selectively worsens the maintenance phase of 2K1C Goldblatt hypertension and support the notion that B2R-deficient mice exhibit an impaired ability to release NO in response to elevations of ANG II levels. Chronic administration of an AT2 receptor blocker did not modify the course of 2K1C Goldblatt hypertension in either B2R-/- or B2R+/+ mice. Therefore, the role of AT2 receptors in B2R-mediated protection against ANG II-dependent hypertension remains uncertain.

Genetic inactivation of the B2 receptor in mice worsens two-kidney, one-clip hypertension

Objective Previous studies have suggested that activation of angiotensin II (ANG II) type 2 (AT2) receptors results in nitric oxide (NO) release via activation of endothelial bradykinin B2 (B2R) receptors. The present study was performed to examine the interplay of AT2 and B2R in the development and maintenance of two-kidney, one-clip (2K1C) Goldblatt hypertension. Methods B2R knockout (B2R−/−) mice and their wild-type controls (B2R+/+) underwent clipping of the right renal artery and were infused with either saline (SAL) or PD 123319, an AT2 receptor antagonist (PD), via an osmotic pump implanted intraperitoneally. Systolic blood pressure (SBP) was measured in conscious mice. On day 27, mean arterial pressure (MAP) responses were measured in response to consecutive blockade of AT2 receptors and NO synthase (NOS). Results A significant and sustained rise in SBP was observed in both 2K1C B2R+/+ and B2R−/− versus sham-operated groups from day 10 to day 24 after clipping. After this time, SBP rose to significantly higher levels in 2K1C/B2R−/− than in 2K1C/B2R+/+ mice. MAP on day 27 was also higher in 2K1C/B2R−/− than 2K1C/B2R+/+ mice. Chronic PD infusion did not alter the course of hypertension in 2K1C/B2R+/+ or 2K1C/B2R−/− mice as compared with saline-infused mice. Likewise, acute PD infusion did not affect MAP in any of the groups. However, acute NOS inhibition caused significantly greater increases in MAP in 2K1C/B2R+/+ and PD/2K1C/B2R+/+ than 2K1C/B2R−/− and PD/2K1C/B2R−/− mice. Conclusions These results indicate that B2R inactivation selectively worsens the maintenance phase of 2K1C Goldblatt hypertension and support the notion that B2R-deficient mice exhibit an impaired ability to release NO in response to elevations of ANG II levels. Chronic administration of an AT2 receptor blocker did not modify the course of 2K1C Goldblatt hypertension in either B2R−/− or B2R+/+ mice. Therefore, the role of AT2 receptors in B2R-mediated protection against ANG II-dependent hypertension remains uncertain.

Comparative Effects of Chromium, Vanadium and Gymnema Sylvestre on Sugar-Induced Blood Pressure Elevations in SHR

Objective: Effects on systolic blood pressure (SBP) of ingesting three agents reported to influence insulin metabolism, i.e., chromium polynicotinate, bis(maltolato)oxovanadium (BMOV), and the herb, Gymnema sylvestre, were assessed simultaneously in spontaneously hypertensive rats (SHR).Methods: In the first study, SHR were fed either a starch, sugar, or sugar diet containing chromium polynicotinate, bis(maltolato)oxovanadium (BMOV), or G. sylvestre. Tail SBP was estimated indirectly and various blood chemistries were measured. TBARS formation was determined in hepatic and renal tissue. In a second study, tail SBP was measured in SHR ingesting diets containing different concentrations of BMOV.Results: Compared to starch, SHR consuming sucrose showed a significant elevation of SBP within days that was maintained for the duration of study. Addition of chromium polynicotinate to the sucrose diet at the beginning of study prevented the sucrose-induced elevation of SBP for 2 weeks, but SBP rose significantly after that. BMOV at high concentrations overcame the sucrose-induced rise in SBP and even decreased SBP below values seen in SHR eating the starch diet, but marked weight loss was noted. A second study examined different concentrations of BMOV. At 0.01% w/w concentration of BMOV, SBP was still significantly decreased, even though SHR did not lose body weight (BW) early on. SHR consuming G. sylvestre showed no change or even elevated SBP. Hepatic thiobarbituric acid reacting substances (TBARS) formation, an estimate of lipid peroxidation, was decreased by chromium polynicotinate and BMOV, and renal TBARS by chromium polynicotinate. Circulating cholesterol concentrations were decreased in the SHR consuming G. sylvestre.Conclusions: Chromium decreases the portion of SBP elevated by high sucrose intake as shown previously, but high levels of sucrose ingestion can eventually overcome this. BMOV overcame sucrose-induced elevation of SBP as well as some of the “genetic hypertension.” Different from chromium, this decrease was not overcome by high levels of dietary sucrose. The significant lowering of cholesterol with G. sylvestre ingestion indicates some effect on metabolism, but G. sylvestre did not lower and even raised SBP.

Increased density of renal amylin binding sites in experimental hypertension.

High-affinity binding sites for the pancreatic beta-cell hormone amylin have been reported in the kidney, and it has been postulated that these sites may be involved in the genesis of hypertension. In the present study, we have used in vivo injection of 125I-amylin and in vitro autoradiographic techniques to assess renal amylin binding in both a genetic and a surgically induced model of hypertension. In the spontaneously hypertensive rat (SHR) at 6 weeks of age, before the rise in systolic blood pressure, there was a 36% increase in density of amylin binding compared with their normotensive counterpart, the Wistar-Kyoto rat (WKY). In SHR, there was a further increase in the density of amylin binding (to 53% greater) as the systolic blood pressure rose between 6 and 12 weeks of age. Histological examination of kidneys from SHR at 12 weeks of age revealed staining for a brush border glycoprotein, normally restricted to the proximal tubules, extending from the urinary pole into half of the epithelial lining of the glomerular capsule. In contrast to WKY, these cells also bound 125I-amylin with high density in SHR. In a rat model of renal ablation and hypertension, systolic blood pressure correlated with the density of 125I-amylin binding in the renal cortex (r=.54, P=.003, n=28). The changes in amylin binding reported here suggest a possible role for this peptide and/or activation of its receptor in the genesis as well as the maintenance of hypertension.

Cardiovascular changes during acute episodic repetitive hypoxic and hypercapnic breathing in rats.

It has been shown that chronic repetitive ambient hypoxia, simulating pulmonary gas disturbances observed in apnoea, leads to systemic hypertension in rats. However, the relative roles of hypoxia (HO), hypercapnia (HC), gas stress and vigilance on the cardiovascular changes have not yet been demonstrated. The aim of this study was to investigate the acute haemodynamic changes observed during the repetitive inhalation of various gas mixtures in rats for HO alone and HO+HC, and to analyse the effects of vigilance and of the stress of gas administration. We studied 6 unanaesthetized Wistar rats chronically instrumented with an aortic catheter. Nitrogen, nitrogen+CO2 mixtures and compressed air were randomly administered in a Plexiglass chamber for 10 s and then flushed by compressed air for 20 s. Two cycles were repeated every min for 10 to 12 min. The inhaled gas fractions (FI,O2,FI,CO2) were monitored by O2 and CO2 analysers. Blood pressure (BP) was measured by a P23XL transducer. The blood gases were analysed by a 1306 IL meter. In control experiments, with compressed air alone, there were no significant acute changes in heart rate (HR) and BP. During HO there were no changes in HR or BP at FI,O2 values from 0.05-0.14, whilst at FI,O2 values from 0-0.05 systolic blood pressure (SBP) rose significantly (+25.3 +/- 25.7 (SD) mmHg) and HR decreased (-93.8 +/- 124.1 bpm). During HOHC, SBP rose (+35.1 +/- 26.4 mmHg) and HR decreased (-139.3 +/- 75.7 bpm), significantly more than in HO alone. SBP was linearly correlated with Pa,O2 during HO (r = 0.53) and also during HOHC (r = 0.44) and was not directly related to Pa,CO2 which has, nevertheless, an additive effect to HO. SBP rose with each challenge significantly more when the rats were awake than when asleep (behavioural sleep). We conclude that in this acute repetitive inhalation model, the rise in SBP is not related to gas stress or to Pa,CO2 but to a decrease in Pa,O2 and is enhanced by wakefulness.

Boiled coffee and blood pressure. A 14-week controlled trial.

The question of whether long-term elimination of coffee from the diet lowers blood pressure has not been settled. Consumption of Scandinavian-style "boiled coffee" is associated with coronary heart disease. However, little is known about the effect of brewing method on the blood pressure-raising potential of coffee. We have studied the effects on blood pressure and heart rate of total elimination of coffee and tea in comparison with drinking boiled coffee consumed as such, or boiled coffee consumed after filtration through paper filter. Thirty-one women and 33 men first consumed 6 cups/day of boiled and filtered coffee for 17 days. Then they were randomly divided into three groups, which for the next 79 days received either unfiltered boiled coffee (caffeine content 860 mg/l), boiled-and-filtered coffee (887 mg caffeine/l), or no coffee, the latter being replaced by fruit juice and mineral water. Total elimination of coffee did not significantly affect blood pressure or heart rate relative to boiled-and-filtered coffee. In subjects who drank boiled coffee, mean ambulant systolic blood pressure rose significantly relative to those who consumed boiled-and-filtered coffee (mean difference +/- SEM, 3.1 +/- 1.1 mm Hg, p = 0.006). This response showed a tendency to be stronger for women (4.5 +/- 1.8 mm Hg) than for men (1.7 +/- 1.2 mm Hg). We conclude that elimination of filtered coffee has no substantial long-term effect on blood pressure, but consumption of unfiltered boiled coffee may cause a slight but significant rise in systolic blood pressure.

Physiologic increase and tracking of blood pressure in schoolchildren.

4343 blood pressure (BP) recordings were obtained in 1575 schoolchildren during 5 years. Systolic BP rose proportionally to upper arm muscle area (MA) in both sexes. In contrast, upper arm fat area (FA) was considerably lower in boys than in girls, and the rise of systolic BP in boys during puberty was not accompanied by any increase of FA. At repeat examination of 900 children after 1 to 5 years, between 35% and 53% of those with initial systolic BP in the highest quintile had again values in the same quintile, thus twice as often as expected. Tracking in the highest decile was even stronger: 37% of 82 children had again systolic BP in the highest decile at 2 years, and 29% at 4 to 5 years. We conclude that the physiologic increase of systolic BP is primarily determined by rising muscle mass, and tracking still remains detectable in children after 4 to 5 years and is strongest in those with highest values.