Moderate Elevation Of Blood Pressure Research Articles

Determining the Relationship Between Blood Pressure, Kidney Function, and Chronic Kidney Disease: Insights From Genetic Epidemiology.

It is well established that decreased kidney function can increase blood pressure (BP), but it is unproven whether moderately elevated BP causes chronic kidney disease (CKD) or glomerular hyperfiltration. 311 119 White British UK Biobank participants were included in logistic regression analyses to estimate the odds of CKD (defined as long-term kidney replacement therapy, estimated glomerular filtration rate [eGFR]< 60mL/min/1.73m2, or urinary albumin:creatinine ratio ≥3 mg/mmol) associated with higher genetically predicted BP using genetic risk scores comprising 219 systolic and 223 diastolic BP loci. Analyses estimating associations with clinical categories of eGFR and urinary albumin:creatinine ratio were also conducted, with an eGFR ≥120 mL (min·1.73m2) considered evidence of glomerular hyperfiltration. 21 623 participants had CKD: 7781 with reduced eGFR and 15 500 with albuminuria. 1828 participants had an eGFR ≥120 mL/min/1.73m2. Each genetically predicted 10 mmHg higher systolic BP and 5 mmHg higher diastolic BP were associated with a 37% (95% CI, 1.29-1.45) and 19% (1.14-1.25) higher odds of CKD, respectively. Associations were evident for both the reduced eGFR and albuminuria components of the CKD outcome. The odds of hyperfiltration (versus an eGFR ≥60 and <90 mL/min/1.73m2 were 49% higher (95% CI, 1.21-1.84) for each genetically predicted 10 mmHg higher systolic BP. Associations with CKD and hyperfiltration were similar irrespective of preexisting diabetes, vascular disease, or different levels of adiposity. In this general population, genetic epidemiological evidence supports a causal role of life-long differences in BP for decreased kidney function, glomerular hyperfiltration, and albuminuria. Physiological autoregulation may not afford complete renal protection against the moderate BP elevations.

Simvastatin therapy attenuates memory deficits that associate with brain monocyte infiltration in chronic hypercholesterolemia

Evidence associates cardiovascular risk factors with unfavorable systemic and neuro-inflammation and cognitive decline in the elderly. Cardiovascular therapeutics (e.g., statins and anti-hypertensives) possess immune-modulatory functions in parallel to their cholesterol- or blood pressure (BP)-lowering properties. How their ability to modify immune responses affects cognitive function is unknown. Here, we examined the effect of chronic hypercholesterolemia on inflammation and memory function in Apolipoprotein E (ApoE) knockout mice and normocholesterolemic wild-type mice. Chronic hypercholesterolemia that was accompanied by moderate blood pressure elevations associated with apparent immune system activation characterized by increases in circulating pro-inflammatory Ly6Chi monocytes in ApoE-/- mice. The persistent low-grade immune activation that is associated with chronic hypercholesterolemia facilitates the infiltration of pro-inflammatory Ly6Chi monocytes into the brain of aged ApoE-/- but not wild-type mice, and links to memory dysfunction. Therapeutic cholesterol-lowering through simvastatin reduced systemic and neuro-inflammation, and the occurrence of memory deficits in aged ApoE-/- mice with chronic hypercholesterolemia. BP-lowering therapy alone (i.e., hydralazine) attenuated some neuro-inflammatory signatures but not the occurrence of memory deficits. Our study suggests a link between chronic hypercholesterolemia, myeloid cell activation and neuro-inflammation with memory impairment and encourages cholesterol-lowering therapy as safe strategy to control hypercholesterolemia-associated memory decline during ageing.

Association between cumulative blood pressure and long-term risk of cardiovascular disease: findings from the 26-year Chinese Multi-provincial Cohort Study-Beijing Project.

Background:Cumulative blood pressure (BP), a measure incorporating the level and duration of BP exposure, is associated with the risk of cardiovascular disease (CVD). However, the level at which cumulative BP could significantly increase the risk remains unclear. This study aimed to investigate the association of 15-year cumulative BP levels with the long-term risk of CVD, and to examine whether the association is independent of BP levels at one examination.Methods:Data from a 26-year follow-up of the Chinese Multi-provincial Cohort Study-Beijing Project were analyzed. Cumulative BP levels between 1992 and 2007 were calculated among 2429 participants free of CVD in 2007. Cardiovascular events (including coronary heart disease and stroke) occurring from 2007 to 2018 were registered. Adjusted hazard ratios (HRs) for CVD incidence associated with quartiles of cumulative systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated.Results:Of the 2429 participants, 42.9% (1042) were men, and the mean age in 2007 was 62.1 ± 7.9 years. Totally, 207 CVD events occurred during the follow-up from 2007 to 2018. Participants with higher levels of cumulative SBP or DBP exhibited a higher incidence rate of CVD (P < 0.001). Compared with the lowest quartile of cumulative SBP, the HR for CVD was 1.03 (95% confidence interval [CI]: 0.59–1.81), 1.69 (95% CI: 0.99–2.87), and 2.20 (95% CI: 1.21–3.98) for the second to the fourth quartile of cumulative SBP, and 1.46 (95% CI: 0.86–2.48), 1.99 (95% CI: 1.18–3.35), and 2.08 (95% CI: 1.17–3.71) for the second to the fourth quartile of cumulative DBP, respectively. In further cross-combined group analyses with BP measurements in 2007, 15-year cumulative BP levels higher than the median, that is, 1970.8/1239.9 mmHg·year for cumulative SBP/DBP, which were equivalent to maintaining SBP/DBP levels of 131/83 mmHg or above on average in 15 years, were associated with higher risk of CVD in subsequent years independent of BP measurements at one-time point.Conclusion:Cumulative exposure to moderate elevation of BP is independently associated with increased future cardiovascular risk.

Adverse pregnancy outcomes associated with moderate elevations in blood pressure or blood glucose in Ugandan women; a prospective cohort study

BACKGROUNDThe association between overt hypertension and diabetes and adverse pregnancy outcomes is well documented. Recent evidence suggests that even moderate elevations in blood pressure or blood glucose may confer a significant risk in a dose-dependent manner. However, these studies have primarily been undertaken in white populations in high-income settings. Hypertension and diabetes are emerging as major public health issues in sub-Saharan Africa as the region undergoes rapid urbanization. It is therefore important to understand how such noncommunicable conditions contribute to pregnancy outcomes in these populations.OBJECTIVEThis study aimed to determine the association between stage 1 hypertension or fasting blood glucose in the gestational diabetes mellitus-range and adverse pregnancy outcomes in Uganda, and to describe the effects of other contributing factors such as maternal obesity.STUDY DESIGNThis was a prospective cohort study of 2857 women at 5 major hospitals in urban and semiurban central Uganda. Women were enrolled at 24 to 28 weeks’ gestation. Data about the maternal demographics, anthropometrics, fasting venous blood glucose, blood pressure, and pregnancy outcomes were collected. Moderate elevations in blood pressure and blood glucose were defined using the latest American College of Cardiology and American Heart Association definition of stage 1 hypertension and the World Health Organization's criteria for fasting blood glucose in the gestational diabetes mellitus-range. The primary outcomes of interest were perinatal death and large birthweight for gestational age, and the secondary outcomes were preterm birth, cesarean delivery, and neonatal admission. A multivariable logistic regression analysis was used.RESULTSStage 1 hypertension increased the odds of perinatal death by more than 2-fold (adjusted odds ratio, 2.68; 95% confidence interval, 1.36–5.29), with a positive but insignificant association with preterm birth. Hyperglycemia in the gestational diabetes mellitus-range was associated with cesarean delivery only (adjusted odds ratio, 1.65; 95% confidence interval, 1.20–2.27). Maternal obesity increased the risk of having large birthweight babies (adjusted odds ratio, 2.30; 95% confidence interval, 1.74–3.02), a cesarean delivery (adjusted odds ratio, 2.75; 95% confidence interval, 2.17–3.48), and neonatal admission (adjusted odds ratio, 1.63; 95% confidence interval, 1.16–2.30).CONCLUSIONModerate elevations in blood pressure and maternal obesity are stronger predictors of adverse maternal and neonatal outcomes than moderate elevations in blood glucose levels and should be the focus of intervention in these resource-poor settings. Further research is needed to determine the cost-effectiveness of identifying and managing moderate elevations in blood pressure and maternal obesity.

Geoffrey Rose's Strategy of Prevention Applied to COVID-19.

Geoffrey Rose's Strategy of Prevention Applied to COVID-19.

Safety and pharmacokinetics of BXQ-350 in a phase 1a and 1b trial of solid tumors and high-grade glioma.

e13531 Background: BXQ-350 is composed of the multifunctional, lysosomal-activator protein Saposin C and phosphatidylserine lipid with demonstrated antitumor effects in vitro and in vivo. In this abstract we update the safety and pharmacokinetic (PK) profile based on an ongoing Phase 1 trial. Methods: BXQ-350 was administered in a Phase 1a dose-escalation trial (NCT02859857), and an ongoing Phase 1b trial (data cut off at max of 6 cycles, 01DEC2018) to refractory solid tumor/high-grade glioma patients (pts). In Phase 1a, pts received escalating IV BXQ-350 doses of 0.7, 1.1, 1.4, 1.8, or 2.4 mg/kg on days 1, 2, 3, 4, 5, 8, 10, 12, 15, 22 (cycle 1), 29 (cycle 2), and thereafter 28-day cycles. PK was assessed over a 24-hr period following the first dose. The Saposin C level was analyzed by ELISA and PK parameters were calculated using noncompartmental methods. Results: The 1a cohort of 18 pts (age 24-69) had a median of 3 cycles and 1b cohort of 20 pts (age 31-80) had median of 2 cycles with no treatment-related serious adverse events to date. Moderately severe related adverse events (AEs, n case, n events) are reported with serious non-related events. The most common treatment-related AE was fatigue (2 at dose 1.1, 2 at 1.8, 1 at 2.4mg/kg and 3 in 1b), at 2.4 mg/kg, 1 pt had moderate blood pressure elevation. Exposures in the 1.4 and 1.8 mg/kg cohorts were less than dose-proportional, likely due to higher clearance in those groups. The overall mean clearance and half-live values were 66.8 (mL/kg/h) and 4.03 h, respectively. Conclusions: BXQ-350 has had no serious related AEs during dose-escalation or in the on-going trial supporting a tolerable safety profile at 2.4 mg/kg. Clinical trial information: NCT02859857. [Table: see text]

Changes in Blood Pressure and Urine Albumin-Creatinine Ratio in a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema.

PurposeTo compare blood pressure and urine albumin-creatinine ratio over time for participants receiving aflibercept, bevacizumab, or ranibizumab.MethodsPreplanned secondary analyses from a randomized trial comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME). The Diabetic Retinopathy Clinical Research Network (DRCR.net) enrolled 660 participants with DME and visual acuity 20/32 or worse in at least one eye. Eyes received intravitreous injections of 2.0 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab based on a structured retreatment protocol over 2 years. Main outcome measures were (1) a change in blood pressure at 2 years, and (2) a change in urine albumin-creatinine ratio (UACR) at 1 year.ResultsAt baseline, 95 participants (14%) had normal blood pressure, 220 (33%) had borderline blood pressure elevation, 206 (31%) had mild blood pressure elevation, and 139 (21%) had moderate blood pressure elevation. Average change in mean arterial pressure from baseline to 2 years was −1.2 ± 15, −1.8 ± 13.5, −2.6 ± 14.4 mm Hg in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.69). At baseline 247 participants (38%) had no albuminuria (<30 mg/g), 195 (30%) had microalbuminuria (30–300 mg/g), and 212 (32%) had macroalbuminuria (>300 mg/g). Changes in UACR category were not different among treatment groups at the 52-week visit (global P = 0.29).ConclusionsThere do not appear to be treatment group differences for changes in blood pressure or UACR as a reflection of kidney function in patients with DME treated with aflibercept, bevacizumab, or ranibizumab.

Moving Beyond Office Blood Pressure to Achieve a Personalized and More Precise Hypertension Management: Which Way to Go?

Blood pressure (BP) has a well-documented, continuous relationship with cardiovascular risk,1 and hypertension has a huge impact at population level in terms of cardiovascular complications and mortality.2 On the other hand, BP reduction in hypertensive subjects is easily achievable and provides dose-dependent prognostic benefits.3 While evidence from large-scale trials represents the backbone for clinical decisions, physicians must strive to achieve a personalized approach to disease management in individual subjects, including those with hypertension and cardiovascular diseases. Indeed, current use of terms such as personalized or precision medicine refers to patients’ care guided by individual molecular characteristics combined with up-to-date diagnostic methods. Specifically, when considering hypertension management, it has been proposed that the intensity of BP lowering should be personalized according to individual cardiovascular risk profile, meaning that (1) prompt BP control should mainly be achieved in high-risk patients; and (2) achievement of lower BP levels may be beneficial in subjects at higher cardiovascular risk. Evidence is available that in high-risk individuals, absolute benefits of treatment are greatest, and pharmacological treatment is more cost-effective.4 On the other hand, when targeting high-risk hypertensive subjects, the large reduction of absolute cardiovascular risk obtained by treatment is accompanied by a considerable residual risk. The latter represents the excess of risk due to the presence of irreversible organ damage, which persists even after achieving optimal control of BP and other risk factors.5 On the contrary, an effective BP reduction by treatment obtained earlier in the clinical history of hypertension, that is in still low-risk individuals, leaves much less residual risk and, thus, offers more solid lifelong cardiovascular protection.5 This kind of reasoning supports the importance of achieving effective and early BP control also in subjects with mild–moderate BP elevations and low cardiovascular risk. Whether lower BP targets are justified …

L-Arginine and B vitamins improve endothelial function in subjects with mild to moderate blood pressure elevation

PurposeThe aim of this trial was to investigate the influence of a dietetic product consisting of a unique combination of l-arginine with the vitamins B6, folic acid and B12 (Telcor® Arginin plus) on endothelial dysfunction.MethodsSubjects aged 40–65 years with mild to moderate blood pressure (BP) elevation not treated with anti-hypertensive drugs were randomly assigned to either the dietetic product (n = 40) or a matching placebo (n = 41) for 3 months with open follow-up for a further 3 months. Postprandial change in endothelial function was assessed using the validated reactive hyperaemia index (RHI) at 3 months compared to the study onset (RHI post–pre, visit 3–visit 1; ΔΔRHI). Secondary parameters included BP and plasma homocysteine concentration.ResultsThe primary efficacy analysis revealed superiority of the nutritional intervention over placebo (p = 0.0349) in reducing the deterioration of endothelial function. While in the active group ΔΔRHI increased (0.371 ± 0.122), almost no change could be detected in the placebo group (0.031 ± 0.100), thus demonstrating a significant improvement in vascular function in the intervention group. Moreover, the intervention reduced BP and homocysteine levels. Non-serious adverse events were equally distributed in both groups, and none of the events were assessed as possibly intervention-related by the investigators.ConclusionsThis trial confirmed the effective and safe use of dietary management with l-arginine in combination with B vitamins. The primary efficacy analysis demonstrated a statistically significant superiority of the combination of l-arginine with B vitamins over placebo in improving and restoring impaired endothelial function and lowering BP in patients with mild to moderate blood pressure elevation.

Acute and chronic role of nitric oxide, renin-angiotensin system and sympathetic nervous system in the modulation of calcium sensitization in Wistar rats.

Principal vasoactive systems - renin-angiotensin system (RAS), sympathetic nervous system (SNS), nitric oxide (NO) and prostanoids - exert their vascular effects through the changes in calcium levels and/or calcium sensitization. To estimate a possible modulation of calcium sensitization by the above vasoactive systems, we studied the influence of acute and chronic blockade of particular vasoactive systems on blood pressure (BP) changes elicited in conscious normotensive rats by acute dose-dependent administration of Rho-kinase inhibitor fasudil. Adult male chronically cannulated Wistar rats were used throughout this study. The acute inhibition of NO synthase (NOS) by L-NAME enhanced BP response to fasudil, the effect being considerably augmented in rats deprived of endogenous SNS. The acute inhibition of prostanoid synthesis by indomethacin modified BP response to fasudil less than the acute NOS inhibition. The chronic NOS inhibition caused moderate BP elevation and a more pronounced augmentation of fasudil-induced BP changes compared to the effect of acute NOS inhibition. This indicates both short-term and long-term NO-dependent attenuation of calcium sensitization. Long-term inhibition of RAS by captopril caused a significant attenuation of BP changes elicited by fasudil. In contrast, a long-term attenuation of SNS by chronic guanethidine treatment (in youth or adulthood) had no effect on BP response to fasudil, suggesting the absence of SNS does not affect calcium sensitization in vascular smooth muscle of normotensive rats. In conclusion, renin-angiotensin system contributes to the long-term increase of calcium sensitization and its effect is counterbalanced by nitric oxide which decreases calcium sensitization in Wistar rats.

Mild DOCA-salt hypertension: sympathetic system and role of renal nerves

Excess sympathetic nervous system activity (SNA) is linked to human essential and experimental hypertension. To test whether sympathetic activation is associated with a model of deoxycorticosterone acetate (DOCA)-salt hypertension featuring two kidneys and a moderate elevation of blood pressure, we measured whole body norepinephrine (NE) spillover as an index of global SNA. Studies were conducted in chronically catheterized male Sprague-Dawley rats drinking water containing 1% NaCl and 0.2% KCl. After a 7-day surgical recovery and a 3-day control period, a DOCA pellet (50 mg/kg) was implanted subcutaneously in one group of rats (DOCA), while the other group underwent sham implantation (Sham). NE spillover was measured on control day 2 and days 7 and 14 after DOCA administration or sham implantation. During the control period, mean arterial pressure (MAP) was similar in Sham and DOCA rats. MAP was significantly increased in the DOCA group compared with the Sham group after DOCA administration (day 14: Sham = 109 ± 5.3, DOCA = 128 ± 3.6 mmHg). However, plasma NE concentration, clearance, and spillover were not different in the two groups at any time. To determine whether selective sympathetic activation to the kidneys contributes to hypertension development, additional studies were performed in renal denervated (RDX) and sham-denervated (Sham-DX) rats. MAP, measured by radiotelemetry, was similar in both groups during the control and DOCA treatment periods. In conclusion, global SNA is not increased during the development of mild DOCA-salt hypertension, and fully intact renal nerves are not essential for hypertension development in this model.

Pathophysiology of hypertensive renal damage: implications for therapy.

Unlike the majority of patients with uncomplicated hypertension in whom minimal renal damage develops in the absence of severe blood pressure (BP) elevations, patients with diabetic and nondiabetic chronic kidney disease (CKD) exhibit an increased vulnerability to even moderate BP elevations. Investigations in experimental animal models have revealed that this enhanced susceptibility is a consequence of an impairment of the renal autoregulatory mechanisms that normally attenuate the transmission of elevated systemic pressures to the glomeruli in uncomplicated hypertension. The markedly lower BP threshold for renal damage and the steeper slope of relationship between BP and renal damage in such states necessitates that BP be lowered into the normotensive range to prevent progressive renal damage. When BP is accurately measured using radiotelemetry in animal models, the renal protection provided by renin-angiotensin system (RAS) blockade is proportional to the BP reduction with little evidence of BP-independent protection. A critical evaluation of the clinical data also suggests that the BP-independent renoprotection by RAS blockade has been overemphasized and that achieving lower BP targets is more important than the selection of antihypertensive regimens. However, achievement of such BP goals is difficult in CKD patients without aggressive diuresis, because of their proclivity for salt retention. The effectiveness of RAS blockers in lowering BP in patients who have been adequately treated with diuretics, along with their potassium-sparing and magnesium-sparing effects, provides a more compelling rationale for the use of RAS blockade in the treatment of CKD patients than any putative BP-independent renoprotective superiority.

Cyclooxygenases, the Kidney, and Hypertension

Selective cyclooxygenase (COX)-2 inhibitors that are in widespread clinical use were developed to avoid side effects of conventional NSAIDs, including gastrointestinal and renal toxicity. However, COX-2 is constitutively expressed in the kidney and is highly regulated in response to alterations in intravascular volume. COX-2 metabolites have been implicated in maintenance of renal blood flow, mediation of renin release, and regulation of sodium excretion. COX-2 inhibition may transiently decrease urine sodium excretion in some subjects and induce mild to moderate elevation of blood pressure. Furthermore, in conditions of relative intravascular volume depletion and/or renal hypoperfusion, interference with COX-2 activity can have deleterious effects on maintenance of renal blood flow and glomerular filtration rate. In addition to physiological regulation of COX-2 expression in the kidney, increased renal cortical COX-2 expression is seen in experimental models associated with altered renal hemodynamics and progressive renal injury (decreased renal mass, poorly controlled diabetes), and long-term treatment with selective COX-2 inhibitors ameliorates functional and structural renal damage in these conditions.

Baroreflex Control of Heart Rate in Young and Adult Salt Hypertensive Inbred Dahl Rats

Baroreflex control of heart rate was studied in inbred salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats that were subjected to chronic dietary sodium chloride loading (for 4 weeks) either in youth or only in adulthood, i.e. from the age of 4 or 12 weeks. Using phenylephrine administration to pentobarbital-anesthetized male rats we have demonstrated the decreased baroreflex sensitivity (lower slope for reflex bradycardia) in young prehypertensive SS/Jr rats fed a low-salt diet as compared to age-matched SR/Jr animals. High salt intake further suppressed baroreflex sensitivity in young SS/Jr but not in SR/Jr rats. Baroreflex sensitivity decreased with age in SR/Jr rats, whereas it increased in SS/Jr rats fed a low-salt diet. Thus at the age of 16 weeks baroreflex sensitivity was much higher in SS/Jr than in SR/Jr animals. High salt intake lowered baroreflex sensitivity even in adult SS/Jr rats without affecting it in adult SR/Jr rats. Nevertheless, baroreflex sensitivity was significantly lower in young SS/Jr rats with a severe salt hypertension than in adult ones with a moderate blood pressure elevation. It is concluded that the alterations of baroreflex sensitivity in young inbred SS/Jr rats (including the response to high salt intake) are similar to those described earlier for outbred salt-sensitive Dahl rats. We have, however, disclosed contrasting age-dependent changes of baroreflex sensitivity in both inbred substrains of Dahl rats.

Effects of chronic treatment with (+)-nicotine on the stress-induced hypertension and downregulation of central nicotinic receptors in rats Comparative study with (−)-nicotine

The effects of chronic treatment with (+)-nicotine on the immobilization stress-induced changes in blood pressure, body weight, and [ 3H]cytisine binding to brain nicotinic receptors were examined in rats and were compared with those of (−)-nicotine. Immobilization stress (2 hr/day −1, for 2 weeks) induced a moderate elevation of blood pressure, loss of body weight gain, and downregulation of [ 3H]cytisine binding sites in cerebral cortex and midbrain. Chronic treatment with (+)- or (−)-nicotine inhibited the stress-induced hypertension but did not suppress the inhibition of body weight gain by stress. Body weight before stress load was also reduced by (−)-nicotine but not (+)-nicotine treatment. Treatment with each isomer increased the maximum number of [ 3H]cytisine binding sites (B max) of brain stem, cerebral cortex, and hippocampus. The B max in midbrain was also increased by (+)-nicotine but not by (−)-nicotine. Stress-induced downregulation in cerebral cortex was inhibited by both isomers. These results suggest that (+)- and (−)-nicotine cause various effects, including anti-stress effect, on the central nervous system in rats, which are slightly different between the isomers.

Relationship between 24-Hour Ambulatory Blood Pressure and Cognitive Function in Healthy Elderly People

This study explored the relationship between cognitive function and blood pressure (BP) in 84 women and 64 men, aged 55–79. Assessments were made of casual BP, 24-hour ambulatory BP, and cognitive function. Participants had no evidence of any health disorders, were taking no medication, and were primarily normotensive. By means of principal components analysis, the number of variables was reduced to three BP components of Level, Wake Variability, and Sleep Variability and four cognitive components of Psychomotor Speed/Cognitive Flexibility, Attention, Verbal Memory, and Short-term/Working Memory. Elevated ambulatory BP (level and variability) was associated with difficulties in Attention and Short-term/Working Memory. The fact that increased risk of poorer cognitive function may be related to BP in an elderly population with relatively low BP means that even moderate elevations in BP may be cause for concern.

Effects of propranolol and atenolol on immobilization stress-induced hypertension and down-regulation of central β-adrenoceptors in rats

Effects of chronic treatment with propranolol or atenolol on stress-induced changes in blood pressure, body weight and cerebral β-adrenoceptors in rats were examined and compared with the effects of chronic treatment with prazosin. Immobilization stress (2 h daily for 2 weeks) induced a moderate elevation of blood pressure, loss of body weight gain and downregulation of cerebral β-adrenoceptors, but produced no changes in the cerebral α 1-adrenoceptors. Chronic administration of propranolol (5 or 50 mg · kg −1), atenolol (5 or 50 mg · kg −1) or prazosin (2 or 20 mg · kg −1) inhibited stress-induced hypertension but did not affect loss of body weight gain. Propranolol increased the density of cerebral β-adrenoceptors by 77% and reduced the downregulation induced by stress. Atenolol also increased the density of cerebral β-adrenoceptors by 34% and abolished the stress-induced downregulation in cerebral β-adrenoceptor density. In contrast, prazosin had no effect on the cerebral β-adrenoceptors in nonstressed or stressed rats. These results suggest that the antihypertensive action of propranolol and atenolol may be partly associated with the inhibition of stress-activated central β-adrenoceptor transmission.

拘束ストレスによるラット脳内&amp;beta;-アドレナリン受容体の変動と高血圧

Effects of chronic treatment with propranolol or atenolol on stress-induced changes in blood pressure and cerebral β-adrenoceptors were examined in rats. Immobilization stress (2 h daily for 2 weeks) induced a moderate elevation of blood pressure and downregulation of cerebral β-adrenoceptors. Chronic administration of propranolol (5 mg•kg-1) or atenolol (5 mg•kg-1) inhibited stress-induced hypertension. Propranolol and atenolol increased the density of cerebral β-adrenoceptors and inhibited the downregulation induced by stress. These results suggest that the antihypertensive action of propranolol and atenolol may be partly associated with the inhibition of stress-activated central β-adrenoceptor transmission.

Stress and Hypertension

Mental stress seems clearly and inextricably linked to the development and maintenance of high blood pressure. Blood pressure evaluated during ambulation, work, or mental stress instead of at rest or in the physician's office consistently improves the ability to predict the target-organ damage often associated with all forms of hypertension. An improved understanding of the relationship between emotional arousal and high blood pressure has accelerated knowledge surrounding the stress-related entities of white-coat hypertension, borderline or mild hypertension, circadian blood pressure changes, labile hypertension, and ambulatory or work-related hypertension. Further development and refinement of diagnostic testing devices such as ambulatory blood pressure monitors and standardized mental stress testing protocols with simultaneous blood pressure determination should improve the evaluation of the diagnostic accuracy, therapeutic efficacy, and prognostic significance associated with stress-related blood pressure elevations. These advances may be especially important because most of the morbidity and mortality associated with hypertension is seen in those with only mild to moderate elevations in blood pressure. Pharmacologic intervention directed at stress-related hypertensive entities may be helpful but remains controversial. Certainly, if instituted, drug therapy should be directed toward preservation of the target organs. Therapeutic intervention through nonpharmacologic modalities appears to be the logical treatment of choice for these hypertensive subgroups. Combined hygienic interventions may be especially powerful. Combinations of lifestyle treatment modalities optimizing nutrition, exercise, weight control, and stress management should obviate the need for medications in many cases of stress-related hypertension. Improved recognition and clinical evaluation of the relationship between environmental stress and hypertension will assist the primary care physician in the management of the blood pressure variations associated with daily life.

Cardiopulmonary receptor regulation of renin release

Cardiopulmonary receptors have been shown to modulate renin release in animals. However, their involvement in reflex control of renin in humans has never been unequivocally established. This report reviews data on the effects on plasma renin activity of maneuvers (lower body negative pressure and passive leg raising) that reduce and increase central venous pressure and cardiac diameter without affecting blood pressure and heart rate, thereby deactivating and stimulating cardiopulmonary receptors with little or no involvement of the arterial baroreceptors. In normotensive subjects, reduction in central venous pressure was accompanied by an increase in plasma renin activity that was similar to the increase observed during tilt that reduced central venous pressure to a similar extent. Conversely, an increase in central venous pressure was accompanied by a reduction in plasma renin activity. The increase in plasma renin activity that followed the reduction in central venous pressure was drastically attenuated in four patients who had undergone cardiac transplantation, along with other reflex effects (changes in forearm vascular resistance and plasma norepinephrine) of cardiopulmonary receptor manipulations. There was a modest reduction in the overall reflex changes in plasma renin activity in patients with mild to moderate essential hypertension compared with normotensive subjects. However, patients with essential hypertension and cardiac hypertrophy showed marked attenuation of all reflex influences of the cardiopulmonary receptors. In five subjects, therapeutic regression of this structural alteration was associated with a clear improvement in the cardiopulmonary reflex. Thus, in humans, cardiopulmonary receptors exert an important reflex control of renin release. This control (which is due in part to receptors located in the cardiac walls) is moderately affected by a mild to moderate blood pressure elevation but is markedly impaired when the elevation produces structural alterations in the heart. Preliminary evidence, however, suggests that the cardiopulmonary reflex may be improved by a reduction in cardiac hypertrophy.