Mm Hg Decrease In Blood Pressure Research Articles

The Distance Monitoring of Blood Pressure as a Tool for Improving of the Quality of Follow-Up Observation of Patients with Arterial Hypertension

This article focuses on the distant blood pressure monitoring for patients with arterial hypertension. As numerous studies show, even slightly elevated blood pressure significantly raises the risk of cardiovascular complications. And, vice versa, a 5 mmHg decrease in blood pressure reduces the lethality risk. Therefore, it is not enough to prescribe the right medication but also it is of paramount importance to monitor patients’ compliance with the treatment. Clinical observation of patients with arterial hypertension is an effective tool for the prevention of cardiovascular complications. However, to date, the coverage of follow-up and the achievement of blood pressure targets in patients with arterial hypertension is one of the most problematic aspects. Distance monitoring of blood pressure opens more opportunities for the doctor’s involvement, timely assessment and adjustment of the medication. The results of domestic and foreign research show high efficacy of the distance blood pressure monitoring. Positive results regarding the achievement of target blood pressure after 3 months are shown when using the technology of blood pressure monitoring and distance counseling of patients with arterial hypertension. In particular, the article considers the technology of mobile health care (mHealth), which is a more flexible platform for a patient’s continuous self-care.

Taking small steps towards targets - perspectives for clinical practice in diabetes, cardiometabolic disorders and beyond

Big changes are hard. When trying to achieve guideline targets in diabetes and cardiometabolic disorders, patients can lack commitment or suffer despondency. It is much easier to make small changes in lifestyle or treatment, which are less noticeable and easier to manage long-term. Obesity is central to the cardiometabolic disorders, and even small weight losses of 2-5% can improve the cardiometabolic risk profile and substantially reduce the risk of developing type 2 diabetes. Likewise, small increases in physical activity, such as 15-30 min of brisk walking per day, can cut the risk of heart disease by 10%. Lifestyle or treatment changes that lead to small improvements in metabolic parameters also impact patient outcome - for example, a 5 mmHg decrease in blood pressure can translate into significant reductions in the rates of myocardial infarction and cardiovascular mortality. Benefits of small changes can also be seen in health economic outcome models. Implementing change at an individual versus a population level has different implications for overall benefit and patient motivation. Even very small steps taken in trying to reach guideline targets should represent a positive achievement for patients. Patient engagement is essential - only when patients commit themselves to change can benefits be maintained, and physicians should recognise their influence. Small changes in individual parameters can result in significant beneficial effects; however, a major impact can occur when small changes are made together in multiple parameters. More research is required to elucidate the full impact of small changes on patient outcome.

Captopril attenuates hypertension and renal injury induced by the vascular endothelial growth factor inhibitor sorafenib

Vascular endothelial growth factor inhibitors (VEGFi) are known to cause hypertension and renal injury that severely limits their use as an anticancer therapy. We hypothesized that the angiotensin-converting enzyme inhibitor captopril not only prevents hypertension, but also decreases renal injury caused by the VEGFi sorafenib. Rats were administered sorafenib (20mg/kg per day) alone or in combination with captopril (40mg/kg per day) for 4weeks. Sorafenib administration increased blood pressure, which plateaued by day 10. Concurrent treatment with captopril for 4weeks resulted in a 30mmHg decrease in blood pressure compared with sorafenib alone (155±5 vs 182±6mmHg, respectively; P<0.05). Furthermore, concurrent captopril treatment reduced albuminuria by 50% compared with sorafenib alone (20±8 vs 42±9mg/day, respectively; P<0.05) and reduced nephrinuria by eightfold (280±96 vs 2305±665μg/day, respectively; P<0.05). Glomerular injury, thrombotic microangiopathy and tubular cast formation were also decreased in captopril-treated rats administered sorafenib. Renal autoregulatory efficiency was determined by evaluating the afferent arteriolar constrictor response to ATP. Sorafenib administration attenuated the vasoconstriction to ATP, whereas concurrent captopril treatment improved ATP reactivity. In conclusion, captopril attenuated hypertension and renal injury and improved renal autoregulatory capacity in rats administered sorafenib. These findings indicate that captopril treatment, in addition to alleviating the detrimental side-effect of hypertension, decreases the renal injury associated with anticancer VEGFi therapies such as sorafenib.

Seed-specific expression of truncated OsGAD2 produces GABA-enriched rice grains that influence a decrease in blood pressure in spontaneously hypertensive rats

Gamma-aminobutyric acid (GABA) is a four-carbon amino acid that is commonly present in living organisms and functions as a major inhibitory neurotransmitter in mammals. It is understood to have a potentially anti-hypertensive effect in mammals. GABA is synthesized from glutamate by glutamate decarboxylase (GAD). In plants, GAD is regulated via its calmodulin-binding domain (CaMBD) by Ca2+/CaM. We have previously reported that a C-terminal truncated version of one of the five rice GAD isoforms, GAD2ΔC, revealed higher enzymatic activity in vitro and that its over-expression resulted in exceptionally high GABA accumulation (Akama and Takaiwa, J Exp Bot 58:2699–2607, 2007). In this study, GAD2ΔC, under the control of the rice glutelin promoter (GluB-1), was introduced into rice cells via Agrobacterium-mediated transformation to produce transgenic rice lines. Analysis of the free amino acid content of rice grains revealed up to about a 30-fold higher level of GABA than in non-transformed rice grains. There were also very high levels of various free protein amino acids in the seeds. GABA-enriched rice grains were milled to a fine powder for oral administration to spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). Six weeks of administration showed that transgenic rice brings about a 20 mmHg decrease in blood pressure in two different kinds of SHRs, while there was no significant hypotensive effect in WKYs. These results suggest an alternative way to control and/or cure hypertension in humans with GABA-enriched rice as part of a common daily diet.Electronic supplementary materialThe online version of this article (doi:10.1007/s11248-009-9272-1) contains supplementary material, which is available to authorized users.

Antihypertensive Effects of Sesamin in Humans

Sesamin, one of the lignans contained in sesame, has been considered to have medicinal effects. It has been reported that sesamin suppressed the development of hypertension in rats. In this study, using a double-blind, cross-over, placebo-controlled trial, we investigated the effect of 4-wk administration of sesamin on blood pressure (BP) in mildly hypertensive humans. Twenty-five middle-aged subjects with mild hypertension were divided into two groups, matched by age and body mass index. Twelve subjects were allocated to 4-wk intake of capsules with 60 mg sesamin per day and 13 subjects to 4-wk intake of a placebo (period 1). After a 4-wk washout period, the subjects received the alternative administration for 4 wk (period 2). BP decreased with statistical significance with the administration of sesamin (systolic: 137.6+/-2.2 to 134.1+/-1.7 mmHg, p=0.044, diastolic: 87.7+/-1.3 to 85.8+/-1.0 mmHg, p=0.045), but little changed with the placebo (systolic: 135.0+/-1.8 to 135.1+/-1.7 mmHg, diastolic: 85.9+/-1.2 to 86.6+/-1.2 mmHg). In conclusion, 4-wk administration of 60 mg sesamin significantly decreased BP by an average of 3.5 mmHg systolic BP and 1.9 mmHg diastolic BP. These results suggest that sesamin has an antihypertensive effect in humans. Epidemiological studies suggested that a 2-3 mmHg decrease in BP reduces the rate of cardiovascular diseases; therefore, it is considered that BP reduction achieved by sesamin may be meaningful to prevent cardiovascular diseases.

A nitric oxide-dopamine link pathway in organum vasculosum laminae terminalis of rat brain exerts control over blood pressure.

1. Experiments were carried out to explore the possible role played by the nitric oxide (NO) and dopamine (DA) system in the organum vasculosum laminae terminalis (OVLT) of rat brain in arterial pressure regulation. 2. Intracerebroventricular (ICV) administration of NO donors such as hydroxylamine or sodium nitroprusside (SNP) caused an up to 59 mmHg decrease in blood pressure (BP) and a decrease in DA release (measured by nafion coated carbon fibre electrodes in combination with voltammetry) in the OVLT. In contrast, ICV administration of N(G)-nitro-L-arginine methyl ester (L-NAME; a constitutive NO synthase inhibitor) or 7-nitroindazol (a neuronal NO synthase inhibitor) caused an up to 98 mmHg increase in BP and an increase in DA release in the OVLT. 3. Intra-OVLT injection of amphetamine (0.1 - 0.3 mg), SKF 38393 (a DA D(1) receptor agonist; 0.01 - 0.03 mg), or apomorphine (a DA D(2,3) receptor agonist; 0.01 - 0.03 mg) caused an increase in BP. On the other hand, intra-OVLT injection of SCH23390 (a DA D(1) receptor antagonist; 0.005 - 0.020 mg) or haloperidol (0.005 - 0.020 mg) caused a decrease in BP. 4. The pressor effects induced by intra-OVLT administration of L-NAME were attenuated by pretreatment with intra-OVLT injection of haloperidol, SCF23390, or 6-hydroxydopamine. In the contrast, the hydroxylamine-, 8-Br-cGMP- or SNP-induced depressor effects were attenuated by pretreatment with intra-OVLT injection of amphetamine, SKF 38393 or apomorphine. 5. The data suggest that activation of a NO-DA link pathway within the OVLT of rat brain exerts control over blood pressure.

Central control of blood pressure by nitrergic mechanisms in organum vasculosum laminae terminalis of rat brain.

Experiments were carried out to explore the possible role played by the nitric oxide (NO) system in the organum vasculosum laminae terminalis (OVLT) of rat brain in arterial pressure regulation. Intracerebroventricular (ICV) or intra-OVLT administration of NO donors such as hydroxylamine, sodium nitro-prusside or s-nitro-acetylpenicillamine caused an up to 55 mmHg decrease in blood pressure (BP) but an increase in NO release (measured by porphyrin/nafion coated carbon fibre electrodes in combination with voltammetry) in the OVLT. In contrast, ICV or intra-OVLT administration of N(G)-nitro-L-arginine methyl ester (L-NAME; a constitutive NO synthase inhibitor) caused an up to 45 mmHg increase in BP but a fall in NO release in the OVLT. Compared with the BP responses induced by ICV injection of NO donors or NO synthase inhibitors, the OVLT route of injection required a much lower dose of NO donors or NO synthase inhibitors to produce a similar BP effect. The depressor effects induced by ICV or intra-OVLT administration of NO donors were attenuated by pretreatment with intra-OVLT injection of methylene blue (an inhibitor of guanylate cyclase), haemoglobin (a NO scavenger), L-NAME or spinal transection. On the other hand, the L-NAME-induced pressor effects were attenuated by pretreatment with intra-OVLT injection of L-arginine or spinal transection. The data suggest that activation of cyclic GMP-dependent NO synthase in the OVLT of rat brain causes cyclic GMP-dependent decreases in arterial pressure via inhibiting the sympathetic efferent activity.

Cardiovascular effects of a novel, potent and selective phosphodiesterase 5 inhibitor, DMPPO: in vitro and in vivo characterization.

1. The aim of this study was to investigate the cardiovascular effects of a novel, potent and specific phosphodiesterase 5 (PDE 5) inhibitor, 1,3 dimethyl-6-(2-propoxy-5-methane sulphonylamidophenyl)-pyrazolo[3,4-d]pyrimidin-4-(5H)-one (DMPPO) in phenylephrine-precontracted rat aortic rings and different in vivo rat preparations. 2. DMPPO elicited a concentration-dependent relaxation of rat aortic rings with functional endothelium. DMPPO-induced relaxation was abolished by endothelium removal or pretreatment with the soluble guanylate cyclase inhibitor, methylene blue (10 microM). 3. In aortic rings without endothelium, the potency (pD2= -log10 EC50) of atrial natriuretic peptide (ANP) to induce relaxation increased from 8.13 +/- 0.05 in the absence of DMPPO, to 8.32 +/- 0.05 and 8.52 +/- 0.08 in the presence of 30 nM and 100 nM DMPPO, respectively. Similarly, the potency of sodium nitroprusside (SNP) in inducing relaxation increased from 7.38 +/- 0.07 in the absence of the PDE 5 inhibitor to 8.07 +/- 0.11 and 8.15 +/- 0.08 in the presence of 30 nM and 100 nM DMPPO, respectively. In contrast, relaxation to the adenylate cyclase activator, forskolin, was unchanged by DMPPO (100 nM). 4. In rings without endothelium, DMPPO (100 nM) increased by 2.5 fold intracellular levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP). Moreover, DMPPO (100 nM) potentiated the increases in cyclic GMP levels induced by ANP (30 nM) by 3 fold and SNP (30 nM) by 2.7 fold. Adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels were not modified by DMPPO. 5. In anaesthetized normotensive or spontaneously hypertensive rats (SHR), DMPPO (2 and 5 mg kg-1, i.v.) lowered blood pressure without affecting heart rate. Similarly, in conscious SHR, orally administered DMPPO (5 mg kg-1) induced a 25 mmHg decrease in blood pressure for at least 7 h without modifying heart rate. Meanwhile, urinary cyclic GMP was increased by 50% whereas cyclic AMP remained unchanged. 6. In normotensive anaesthetized rats, sodium nitroprusside (SNP) (i.v. bolus) induced a decrease in blood pressure which rapidly returned to baseline. In DMPPO (1 mg kg-1, i.v.)-treated rats, the hypotensive effects of SNP (10 to 100 micrograms kg-1) were prolonged over time whereas the peak effect was unchanged. 7. In pithed rats, phenylephrine (i.v. bolus) induced dose-dependent increases in blood pressure. Pretreatment with DMPPO (5 mg kg-1, i.v.) partially inhibited the pressor response to phenylephrine (0.3 to 100 micrograms kg-1). 8. In conclusion, the potent and selective PDE 5 inhibitor, DMPPO, produces relaxation in isolated vessels in the presence of a cyclic GMP drive and reduces blood pressure of intact animals. Its high oral bioavailability and long duration of action should make it a useful tool to study the role of cyclic GMP in various biological systems.

Immunological and side effects of low sc recombinant interleukin-2 dose in addition to conventional treatment in relapsed breast and colorectal cancer patients

Thirteen relapsed cancer patients, four of them operated for colorectal and the nine remaining for breast cancer, were cyclically given low subcutaneous (sc) recombinant interleukin-2 (rIL-2) doses in addition to chemo- or hormone therapy. Cycle intervals were 2 or 6 weeks in length, and the number of cycles ranged from one to 14 and from one to six respectively. Tolerance assessed by clinical and laboratory data, eosinophils, lymphocytes (total number), T subpopulations, B lymphocytes and NK cells were the evaluated parameters. One (7.6%) of the 13 studied patients interrupted the first low dose sc rIL-2 cycle due to a hypersensitive reaction. This case showed relapse from breast cancer. During further cycles, three patients (25%), one operated on for colorectal and two others for breast cancer of the 12 remaining cases who completed all rIL-2 cycles showed an increase in glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), gamma-gt, and creatininemia without any clinical symptoms. A slight influenza-like syndrome and 10-20 mmHg decrease in blood pressure sporadically occurred in all patients under rIL-2 therapy. In both cancer types, a significant (P < 0.05 - P < 0.001) increase in lymphocytes, eosinophils. T4 and T3 subpopulations but not in T8 subpopulations and NK cells occurred at the end of the rIL-2 cycles. In 11 of the 13 patients responsive to conventional therapy, a highly significant increase (P < 0.001) in all parameters apart from B lymphocytes and T4/T8 ratio was observed, while in three cases which were no longer responsive and in another case which had never been responsive to conventional therapy, a slightly significant increase in eosinophils only occurred (P < 0.05). Three colorectal cancer patients showed a partial response and the last a complete response to conventional therapy. In these four patients, time to progression during rIL-2 cycles ranged from 2.5-5 months and the duration of response ranged from 8-19 months. In seven of the eight breast cancer patients who completed all rIL-2 cycles, the response ranged from 3-51+ months and in the last case, which was not responsive to conventional therapy, the disease progressed in spite of the addition of rIL-2. These data suggest that: a) rIL-2 is likely to constitute a well-tolerated and suitable home therapy even when cyclically given for a prolonged period; b) following rIL-2 administration, eosinophils and lymphocytes increase in addition to the T subpopulations.

Attenuated blood pressure responsiveness during post-exercise hypotension.

To test the hypotheses that acute treadmill exercise would produce post-exercise hypotension (PEH) and that PEH would be associated with reduced mean arterial pressure (MAP) responsiveness to the alpha 1-adrenergic agonist phenylephrine. Arterial and venous catheters were implanted into exercise-trained female Dahl-salt sensitive rats (n = 9) for measurement of pulsatile blood pressure (BP) and heart rate (HR). The changes in BP following ganglionic blockade (hexamethonium/atropine) and the MAP responses to phenylephrine (PE) injections after ganglionic blockade (GB) were examined on separate days in testing cages (control) and following 40 min of treadmill exercise (post-ex). Thirty minutes following graded treadmill exercise (20-40 m/min, 0% grade, 40 min duration) blood pressure was significantly reduced (-9 +/- 1) mmHg compared to control. After exercise, GB produced a 43 +/- 3 mmHg decrease in BP which tended (p = 0.08) to be less than the reduction observed during control studies (51 +/- 2 mmHg). PE-induced increases in BP were significantly lower post-ex than control for each of the dosages tested (0.5, 1.0 and 2.0 micrograms/kg). These results demonstrate that there is sustained reduction in PE-induced MAP responsiveness which accompanies exercise-induced decreases in blood pressure in the Dahl salt-sensitive rat. Thus, decreased alpha-adrenoceptor responsiveness may contribute to the production of PEH.

Patent Evaluation: Novel Tetralones as Potassium Channel Activators

SummaryNovelty: Novel tetralones are disclosed which are said to be potassium channel activators. These are potentially useful in the treatment of hypertension and asthma.Biology: In vitro activity was determined by measuring the compounds' ability to inhibit noradrenaline-induced contractions of rat portal vein, and resting tension of guinea-pig trachea. In vivo activity was determined by measuring the reduction of blood-pressure in SHR rats. Data are given for twenty-four compounds. 1,2-Dihydro-4-(1,2-dihydro-2-oxo-1-pyridyl)-2,2-dimethyl-1-oxonaphthalene-6-carbonitrile had IC50s of 0.6 and 0.1 μM, respectively, and produced a 97 mmHg decrease in blood pressure at 1 mg/kg po.Chemistry: The syntheses of sixty-five examples and fifty-five intermediates are detailed. The compounds are prepared by the epoxidation of dihydronaphthalene-ones followed by amine-induced epoxide opening. Fourteen compounds are specifically claimed.Structure: