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Biomedical subjects

Peter Friberg

Publications and source records attributed to Peter Friberg.

At least 19 recordsLinked to original sources

Baroreflex effectiveness index and baroreflex sensitivity predict all-cause mortality and sudden death in hypertensive patients with chronic renal failure.

OBJECTIVES: Impaired arterial baroreflex sensitivity (BRS) has been associated with cardiac mortality and non-fatal cardiac arrests after a myocardial infarction. Patients with chronic renal failure (CRF) have a poor prognosis because of cardiovascular diseases, and sudden death is common. The aim of this study was to assess whether BRS or the baroreflex effectiveness index (BEI), a novel index reflecting the number of times the baroreflex is active in controlling the heart rate in response to blood pressure fluctuations, is associated with prognosis in CRF. METHODS: Hypertensive patients with CRF who were treated conservatively, by haemodialysis or peritoneal dialysis were studied. Electrocardiogram and beat-to-beat blood pressures were recorded continuously and BRS and BEI were calculated. Patients were then followed prospectively for 41 +/- 15 months (range 1-64). RESULTS: During follow-up 69 patients died. Cardiovascular diseases and uraemia accounted for the majority of deaths (60 and 20%, respectively), whereas sudden death occurred in 15 patients. In adjunct with established risk factors such as age, diabetes, congestive heart failure and diastolic blood pressure, reduced BEI was an independent predictor of all-cause mortality among CRF patients [relative risk (RR) 0.50, 95% confidence interval (CI) 0.33-0.71 for an increase of one standard deviation in BEI, P < 0.001]. Diabetes and reduced BRS were independent predictors of sudden death (RR 0.29, 95% CI 0.09-0.86 for an increase of one standard deviation in BRS, P=0.022). CONCLUSIONS: Both BEI and BRS convey prognostic information that may have clinical implications for patients with cardiovascular diseases in general.

Baroreflex↗

Increasing peripheral artery intima thickness from childhood to seniority.

BACKGROUND: Using new, very high-resolution ultrasound biomicroscopy, we examined the thickness of artificial layers of silicone and intima thickness (IT) of radial and anterior tibial arteries in healthy subjects and in patients with vascular disease. METHODS AND RESULTS: Silicone layers of varying thicknesses and mesenteric artery specimens obtained from 18 patients undergoing colectomy were measured by both ultrasound biomicroscopy (55 MHz) and morphometry. There was high correlation (r>0.9; P<0.0001) between IT and intima area versus ultrasound biomicroscopy. In 90 healthy subjects (aged between 10 and 90 years), radial and anterior tibial arterial IT and intima-media thickness were measured, as was carotid intima-media thickness in 56 of these subjects. Age was strongly related with both media thickness and IT of both peripheral arteries. Correlations were found between carotid intima-media thickness and both radial and anterior tibial IT/intima-media thickness (r=0.44 to 0.53; P<0.0001). The IT-to-lumen diameter ratio increased with age and was larger at all ages in the anterior tibial artery (0.067+/-0.034) versus the radial artery (0.036+/-0.012; P<0.0001). A thicker radial intimal layer was found in patients with peripheral artery disease. CONCLUSION: This study is the first to our knowledge in humans to show the feasibility of measuring IT of the radial and anterior tibial arteries using very high-resolution ultrasound. IT progresses with age, and the IT-to-lumen diameter ratio is largest in the arteries of the foot. Assessment of IT by ultrasound biomicroscopy may aid in detecting early peripheral vascular abnormalities.

Adolescent↗

Non-invasive assessment of endothelial function: which technique?

OBJECTIVES: The purpose of this study was to compare 3 non-invasive techniques for assessment of endothelial function in adults and children and evaluate their utility in acute inflammation. BACKGROUND: Endothelial dysfunction is a key early event in pre-clinical atherosclerosis. Flow-mediated dilation (FMD), although the established technique, is expensive and technically demanding. Measurements of vascular responses to inhaled salbutamol by pulse wave analysis (PWA) or pulse contour analysis (PCA) are potential alternatives. METHODS: Sixteen adults (mean age 28 years, range 18 to 39) and 16 children (mean age 13 years, range 7 to 17) underwent concurrent vascular function testing on 2 occasions with ultrasound, PWA, and PCA. Eighteen men were also studied before and after typhoid vaccination. RESULTS: Reproducibility of FMD was high in adults and children (coefficient of variation [CV] = 7.1 and 6.3, respectively). Salbutamol responses were more variable with PWA (adults CV = 11.5, children CV = 17.1) and PCA particularly in children (adults CV = 18.2, children CV = 36.3). Flow-mediated dilation (p < 0.001) and PWA with salbutamol (p = 0.03) responses fell after typhoid vaccination, and PCA (p = 0.7) was unchanged. CONCLUSIONS: Vascular dysfunction during acute inflammation can be measured by FMD and by PWA with salbutamol. Flow-mediated dilation is less variable than PWA. Variability of PCA makes this technique currently unsuited to serial measures of endothelial function in children. Flow-mediated dilation remains the most reproducible method.

Adolescent↗

Sympathetic activation and inflammatory response in patients with subarachnoid haemorrhage.

OBJECTIVE: The aim of this study was to evaluate the correlation between sympathetic nervous activation and the immune response in patients following subarachnoid haemorrhage (SAH). DESIGN AND SETTING: Clinical study in a neurosurgical intensive care unit. PATIENTS AND PARTICIPANTS: Fourteen patients with acute non-traumatic SAH were included. Fifteen healthy, age-matched volunteers served as controls for measurement of catecholamine spillover. INTERVENTION: Blood sampling for C3a, C5b-9, IL-6, IL-8 and norepinephrine kinetic determination was made within 48 h, at 72 h and on the 7th-10th day after the SAH. MEASUREMENTS AND RESULTS: SAH patients exhibited a profound increase in the rate of norepinephrine spillover to plasma at 48 h, 72 h and 7-10 days after the insult, 3-4 times that in healthy individuals. The plasma levels of C3a, IL-6 and C5b-9 were significantly elevated at 48 h, at 72 h and 7-10 days after the SAH, but the plasma level of IL-6 decreased significantly 7-10 days after the SAH. There was no relationship between the magnitude of sympathetic activation and the levels of inflammatory markers. CONCLUSIONS: Following SAH a pronounced activation of the sympathetic nervous system and the inflammatory system occurs. The lack of significant association between the rate of spillover of norepinephrine to plasma and the plasma levels of inflammatory markers indicates that the two processes, sympathetic activation and the immune response, following SAH are not quantitatively linked. In spite of a persistent high level of sympathetic activation the plasma level of IL-6 decreased significantly one week after SAH.

Adult↗

Non-invasive real-time imaging of atherosclerosis in mice using ultrasound biomicroscopy.

There are increasing needs to develop imaging techniques to study in vivo vascular morphology and function in various mouse models of atherosclerosis. Using ultrasound biomicroscopy (UBM), we developed and validated a new imaging protocol to follow lesion progression in atherosclerotic mice. ApoE and LDL receptor double knockout mice (DKO) with various degree of atherosclerosis and normal control mice were imaged at the level of the ascending aorta using UBM. Average plaque thickness, as well as plaque area were delineated in the short-axis images, and were subsequently compared with histological measurements. We showed that plaque area at this vascular site was closely correlated to total plaque burden from en face measurement (p<0.0001). UBM-measured plaque thickness and area correlated with indices for histology measures from the same vascular region (p<0.0001 respective p<0.0001). Furthermore, in 16 DKO mice aged from 32 to 35 weeks, UBM showed significantly weekly increases of IMT in the ascending aorta from 0.106+/-0.108 mm at 32 weeks of age to 0.256+/-0.345 mm at 35 weeks of age (p=0.0002). In conclusion, this novel imaging protocol provides us with a non-invasive, accurate and inexpensive way to follow lesion progression in mice in vivo.

Aging↗

Serum phospholipid fatty acids, adipose tissue, and metabolic markers in obese adolescents.

OBJECTIVE: Fatty acid (FA) composition has a role in adipogenesis. The objective was to study serum phospholipid (PL) FAs in adolescents and their relation to abdominal adipose tissue (AT) compartments and metabolic markers. RESEARCH METHODS AND PROCEDURES: Abdominal AT was measured by magnetic resonance imaging and FA pattern was determined in serum PL of 10 obese adolescents (5 females), median age 12.0 years (range, 10.4 to 16.4) and BMI 30.7 (26.8 to 40.4), and 15 lean control subjects (9 females), median age 12.6 years (range, 11.3 to 15.4), and BMI 19.5 (17.1 to 23.4). RESULTS: Obese adolescents had relatively higher levels of saturated FA (SFA) and nervonic acid compared with controls. Serum PL concentration of n-3 polyunsaturated fatty acids (PUFA) was lower in the obese vs. lean females (p = 0.01), including docosahexaenoic acid (DHA) (p = 0.01). The ratios of arachidonic acid to DHA and total n-6/n-3 FA were increased in obese children (p = 0.02 and 0.01, respectively). n-3 PUFAs were inversely correlated to all subcutaneous AT compartments except visceral AT. The homeostasis model assessment index of beta-cell function related inversely to DHA concentration (p = 0.03). All changes were more marked in the females. DISCUSSION: Serum FA pattern in obese adolescents differed significantly from that in age-matched lean controls, reflecting a decrease in n-3 PUFA, especially DHA, and an increase in SFA. The subcutaneous AT, but not visceral AT, correlated to the changes in PUFA and SFA, suggesting an abnormal essential FA metabolism in obese adolescents.

Abdominal Fat↗

Mediterranean-inspired diet lowers the ratio of serum phospholipid n-6 to n-3 fatty acids, the number of leukocytes and platelets, and vascular endothelial growth factor in healthy subjects.

BACKGROUND: Reduced cardiovascular mortality and morbidity have been shown in persons adhering to Mediterranean-inspired diets (MIDs). Although the underlying mechanisms of this association are poorly understood, the importance of increasing dietary amounts of polyunsaturated fatty acids of the n-3 series has been emphasized. OBJECTIVE: We investigated whether a MID provided to healthy subjects would affect 1) the inflammatory process and endothelial indexes such as vasoregulation and vascular endothelial growth factor (VEGF) and 2) serum phospholipid fatty acid composition. DESIGN: A total of 22 subjects (10 women) received a MID or an ordinary Swedish diet (OSD) for 4 wk in a crossover fashion. Concentrations of lipids and fatty acids, high-sensitivity C-reactive protein, and interleukin 6, both before and after lipopolysaccharide stimulation; the number of leukocytes and platelets; and VEGF and monocyte chemoattractant protein 1 were analyzed. RESULTS: The plasma ratio of n-6 to n-3 fatty acids was substantially lower after the MID than after the OSD (x +/- SEM: 4.72 +/- 0.19 and 2.60 +/- 0.17, respectively; P < 0.0001). Neither C-reactive protein nor interleukin 6 concentrations changed significantly after the MID compared with the OSD. The total number of leukocytes and platelets was 10% (P < 0.05) and 15% (P < 0.001) lower, respectively, after the MID than after the OSD. Serum VEGF concentrations were lower after the MID than after the OSD (237 +/- 30 and 206 +/- 25 pg/mL, respectively; P = 0.0014). CONCLUSIONS: A MID reduces the number of platelets and leukocytes and VEGF concentrations in healthy subjects. This may be linked to higher serum concentrations of n-3 fatty acids, which promote a favorable composition of phospholipids.

Adult↗

Vascular resistance and endothelial function in cyclosporine-treated lung transplant recipients.

The majority of patients undergoing solid organ transplantation develop hypertension, to which vasoconstriction and impaired endothelial function have been suggested to contribute. We compared basal vascular resistance and nitric oxide-mediated endothelial-dependent and independent vasoreactivity between cyclosporine-treated lung transplant recipients and healthy subjects. Forearm blood flow was measured by venous occlusion plethysmography at rest and during acetylcholine, glyceryltrinitrate and N(G)-monomethyl-L-arginine acetate (L-NMMA) infusion in 11 lung transplant recipients 3-5 years after transplantation and in eight healthy subjects. Forearm vascular resistance (FVR) was calculated. Plasma levels of endothelin-1 (ET-1) and von Willebrand factor (vWf) were analysed. Basal vascular resistance was 40% lower in transplant recipients than in healthy subjects (P = 0.021). Endothelial-dependent and independent vasodilation did not differ. Plasma levels of ET-1 and vWf were higher in transplant recipients (P = 0.009 and P < 0.001 respectively). There was a significant correlation between ET-1 levels and FVR in healthy subjects (r = 0.83, P = 0.042), but not in transplant recipients (r = -0.14, P = 0.70). The findings oppose the theory of generalized vasoconstriction and impaired endothelial function in the pathogenesis of hypertension after transplantation. Increased plasma levels of ET-1 do not cause increased FVR in lung transplant recipients.

Adult↗

Further insights into the role of angiotensin II in kidney development.

Over the past decade, compelling studies have highlighted the fundamental role of the renin-angiotensin system (RAS) in renal development and long-term control of renal function and arterial pressure. The present review provides an update of the understanding of how the RAS controls nephrogenesis and nephrovascular development. In addition, the investigations linking the perinatal development of RAS inhibition-induced renal dysmorphology and establishment of adult blood pressure are discussed.

Angiotensin II↗

24-h Systolic blood pressure and heart rate recordings in lean and obese adolescents.

OBJECTIVE: We assessed the hypothesis that differences in day and night-time systolic blood pressure (SBP) and heart rate (HR) recordings were smaller in obese versus lean children and adolescents, and whether measurements obtained during a school week or during weekends or holidays influenced these nocturnal falls. We also wanted to determine whether the results were influenced by gender. METHODS: Ambulatory 24-h BP and HR measurements were performed in 80 subjects, 51 girls and 29 boys. Lean (n = 25) and obese (n = 55) subjects were classified according to body mass index (BMI)-standard deviation (SD) criteria. Forty-eight subjects had their 24-h recordings performed during a school week and 32 during leisure time. RESULTS: The SBP nocturnal dipping response was less pronounced in obese subjects (16.2 +/- 6.3 mmHg) compared with lean controls (21.1 +/- 5.7 mmHg) (P < 0.01) of which the girls constituted most of the difference. HR change between day and night was similar in both groups being approximately 15 b/min. A small but statistical negative correlation was observed between BMI-SD and nocturnal fall in SBP (r = -0.3, P = 0.0065). In all subjects, regardless of BMI-SD, daytime SBP was higher when readings were obtained during a school week (123 +/- 7 mmHg) than during weekends or holidays (119 +/- 7 mmHg) (P = 0.029). CONCLUSION: Obese children and adolescents showed smaller nocturnal falls in SBP compared with lean subjects. This pattern may cause increased cardiovascular loading; thus, it may reflect an early sign of high blood pressure development and adds to cardiovascular risk in young obese individuals.

Adolescent↗

Acute response to intracisternal bupivacaine in patients with refractory pain of the head and neck.

Continuous intracisternal infusion of bupivacaine for the management of intractable pain of the head and neck is effective in controlling pain in this patient group. With the catheter tip being located at the height of the C1 vertebral body, autonomic regulatory information may also be influenced by the infusion of bupivacaine. By combining direct sampling of cerebrospinal fluid (CSF), via a percutaneously placed catheter in the cisterna magna, with a noradrenaline and adrenaline isotope dilution method for examining sympathetic and adrenal medullary activity, we were able to quantify the release of brain neurotransmitters and examine efferent sympathetic nervous outflow in patients following intracisternal administration of bupivacaine. Despite severe pain, sympathetic and adrenal medullary activities were well within normal range (4.2 +/- 0.6 and 0.7 +/- 0.2 nmol min(-1), respectively, mean +/-S.E.M.). Intracisternal bupivacaine administration caused an almost instantaneous elevation in mean arterial blood pressure, increasing by 17 +/- 7 mmHg after 10 min (P < 0.01). Heart rate increased in parallel (17 +/- 5 beats min(-1)), and these changes coincided with an increase in sympathetic nervous activity, peaking with an approximately 50% increase over resting level 10 min after injection (P < 0.01). CSF levels of GABA were reduced following bupivacaine (P < 0.05). CSF catecholamines and serotonin, and EEG, remained unaffected. These results show that acutely administered bupivacaine in the cisterna magna of chronic pain sufferers leads to an activation of the sympathetic nervous system. The results suggest that the haemodynamic consequences occur as a result of interference with the neuronal circuitry in the brainstem. Although these effects are transient, they warrant caution at the induction of intracisternal local anaesthesia.

Adult↗

Tubular mitochondrial alterations in neonatal rats subjected to RAS inhibition.

Pharmacological interruption of the angiotensin II (ANG II) type 1 receptor signaling during nephrogenesis in rats perturbs renal tubular development. This study aimed to further investigate tubular developmental defects in neonatal rats subjected to ANG II inhibition with enalapril. We evaluated tubular ultrastructural changes using electron microscopy and estimated spectrophotometrically activity or concentrations of succinate dehydrogenase (SDH), cytochromes a and c, which are components of mitochondrial respiratory chain, on postnatal days 2 and 9 (PD2 and PD9). Renal expression of sodium-potassium adenosinetriphosphatase (Na(+)-K(+)-ATPase) and two reflectors of mitochondrial biogenesis [mitochondrial transcription factor A (TFAM) and translocase of outer mitochondrial membrane 20 (TOM20)] also were studied using Western immunoblotting and immunohistochemistry. Enalapril disrupted inner mitochondrial membranes of developing cortical and medullary tubular cells on PD2 and PD9. These findings were paralleled by impaired mitochondrial respiratory function, as revealed from the changes in components of the mitochondrial respiratory chain, such as decreased cytochrome c level in the cortex and medulla on PD2 and PD9, decreased cytochrome a level in the cortex and medulla on PD2, and diminished cortical SDH activity on PD2 and PD9. Moreover, tubular expression of the most active energy-consuming pump Na(+)-K(+)-ATPase was decreased by enalapril treatment. Renal expression of TFAM and TOM20 was not altered by neonatal enalapril treatment. Because nephrogenesis is a highly energy-demanding biological process, with the energy being utilized for renal growth and transport activities, the structural-functional alterations of the mitochondria induced by neonatal enalapril treatment may provide the propensity for the tubular developmental defect.

Angiotensin II↗

Endothelial dysfunction in childhood infection.

BACKGROUND: Atherosclerosis begins in early life, and endothelial dysfunction is recognized as a key initiating event in the development of atherosclerosis. Although infection has been implicated in endothelial dysfunction and atherogenesis, the impact of acute common childhood infections on the vascular endothelium is unknown. METHODS AND RESULTS: We studied 600 children aged 10 years drawn from the Avon Longitudinal Study of Parents and Children. The children were divided into 3 groups: those with current acute infection (AI; n=135; 73 boys and 62 girls); a convalescent group with infection in the past 2 weeks (n=166; 78 boys and 88 girls), and a healthy control group (n=299; 131 boys and 168 girls). Endothelial function was determined in all subjects by high-resolution ultrasound to measure brachial artery flow-mediated dilation (FMD) and was expressed as the percentage change in diameter from baseline after reactive hyperemia. FMD was repeated in 40 children in the AI group and 50 in the control group after a mean interval of 1 year. FMD was lower in both the AI group (6.3+/-2.7%, mean+/-SD) and the convalescent group (8.1+/-3.1%) than in the control group (9.7+/-2.5%; P<0.001 for both). The observed differences in FMD remained after adjustment for potential confounding variables. At the repeat visit, FMD was unchanged in controls (P=0.85) but improved in the AI group (P<0.001). CONCLUSIONS: Acute infection in childhood is associated with impaired endothelium-dependent vasodilation. These findings support a potential role for previously unsuspected extrinsic inflammatory stimuli in the pathogenesis of early atherosclerosis.

Arteriosclerosis↗

Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure.

AIMS: Although cardiac sympathetic activation is associated with adverse outcome in patients with chronic heart failure (CHF), the influence of renal sympathetic activity on outcome is unknown. We assessed the hypothesis that renal noradrenaline (NA) spillover is a predictor of the combined endpoint of all-cause mortality and heart transplantation in CHF. METHODS AND RESULTS: Sixty-one patients with CHF, New York Heart Association (NYHA) I-IV (66% NYHA III-IV), and left ventricular ejection fraction (LVEF) 26+/-9% (mean+/-SD) were studied with cardiac and renal catheterizations at baseline and followed for 5.5+/-3.7 years (median 5.5 years, range 12 days to 11.6 years). Nineteen deaths and 13 cases of heart transplantation were registered. Only renal NA spillover above median, 1.19 (interquartile range 0.77-1.43) nmol/min, was independently associated with an increased relative risk (RR) of the combined endpoint (RR 3.1, 95% CI 1.2-7.6, P=0.01) in a model also including total body NA spillover, LVEF, glomerular filtration rate (GFR), renal blood flow, cardiac index, aetiology, and age. CONCLUSION: Renal noradrenergic activation has a strong negative predictive value on outcome independent of overall sympathetic activity, GFR, and LVEF. These findings suggest that treatment regimens that further reduce renal noradrenergic stimulation could be advantageous by improving survival in patients with CHF.

Autonomic Nervous System Diseases↗

Reproducibility of methods for assessing baroreflex sensitivity and temporal QT variability in end-stage renal disease and healthy subjects.

Spontaneous baroreflex sensitivity (BRS), the reflex heart rate modulation in response to blood pressure changes (predominantly an index of cardiac vagal activity) and temporal QT variability (an index of myocardial repolarization) have been demonstrated to convey important prognostic information. The information about reproducibility of BRS and temporal QT variability is limited and there is lack of information regarding patients with cardiovascular diseases. We investigated reproducibility of spontaneous BRS using the sequence technique and temporal QT variability index (QTVI) in terms of intra-, interexaminer and within-subject variability in end-stage renal disease patients (ESRD, n=17, age 55+/-14 years) and healthy subjects (HS, n=29, age 32+/-12 years, P<0.01). ECG and blood pressure (Portapres) were recorded on two separate days and BRS and QTVI were evaluated by two independent examiners. The mean heart rate was similar in ESRD patients in comparison to healthy controls, whereas the mean arterial pressure was 13 % higher in ESRD patients (P<0.01). Spontaneous BRS was 62% lower (P<0.01) and QTVI was 41% higher in ESRD patients (P<0.01) compared to healthy subjects, respectively. Coefficient of variation (CV) of within-subject reproducibility of BRS and QTVI measurements was moderate (BRS: 33 % for ESRD, 27% for HS; QTVI: 40% for ESRD, 18% for HS). The 95% limit of within-subject reproducibility of BRS measurements was 3.8 ms/mm Hg for ESRD patients and 8.1 ms/mm Hg for healthy subjects; whereas the 95% limit of reproducibility of within-subject reproducibility of QTVI measurements was 0.73 for ESRD patients and 0.55 for healthy subjects. Concordance correlation coefficients of within-subject variability of BRS and QTVI were between 0.74 and 0.83 in both groups. CV of intra- and inter-examiner reproducibility of BRS and QTVI measurements in both groups ranged between 1 and 11%. In conclusion, the intra- and inter-examiner reproducibility/agreement of BRS and QTVI were high, whereas the within-subject reproducibility of these two methods was moderate, in both ESRD patients and healthy subjects. Thus, small differences in BRS and QTVI in longitudinal/interventional studies should be interpreted with caution.

Adult↗

Reduced baroreflex effectiveness index in hypertensive patients with chronic renal failure.

BACKGROUND: Impaired arterial baroreflex function has been associated with an increased risk of ventricular arrhythmia and sudden death. This has also been suggested for patients with chronic renal failure (CRF) who are at high risk for cardiovascular morbidity. The aim of this study was to investigate the arterial baroreflex function in CRF patients with emphasis on analyzing the time during which the arterial baroreflex is active, the baroreflex effectiveness index (BEI). METHODS: Beat-to-beat blood pressure (measured with Portapres) and electrocardiography were continuously registered during 30 min rest in 216 hypertensive CRF patients on hemodialysis (n=95), continuous ambulatory peritoneal dialysis (n=59), or conservative treatment (n=59). The spontaneous sequence method was used to calculate BRS and BEI. Age-matched healthy subjects (n=43) were examined for comparison. RESULTS: The BRS was reduced by 51% and the BEI by 49% in CRF patients compared with healthy subjects (P<.001 for both). In addition, CRF patients with diabetes showed further reductions compared with patients without diabetes (15% reduction of BRS and 44% of BEI, P<.01 for both). The treatment modality for renal failure had no effect on BRS or BEI. In a multivariate linear regression analysis, age, body mass index, and systolic blood pressure were independent predictors of BRS, whereas age and diabetes were independent predictors of BEI in patients with CRF. CONCLUSIONS: We conclude that BEI, which is markedly reduced in hypertensive patients with CRF, may convey information on arterial baroreflex function that is complementary to BRS.

Antihypertensive Agents↗