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RESEARCH Open AccessHigh blood pressure, antihypertensive medicationand lung function in a general adult populationEva Schnabel1,2*, Stefan Karrasch3,4,5, Holger Schulz1,3,5, Sven Gläser6, Christa Meisinger7,11, Margit Heier7,11,Annette Peters8,11, H-Erich Wichmann1,8, Jürgen Behr5,9, Rudolf M Huber5,10and Joachim Heinrich1, forfor the Cooperative Health Research in the Region of Augsburg (KORA) Study GroupAbstractBackground: Several studies showed that blood pressure and lung function are associated. Additionally, apotential effect of antihypertensive medication, especially beta-blockers, on lung function has been discussed.However, side effects of beta-blockers have been investigated mainly in patients with already reduced lungfunction. Thus, aim of this analysis is to determine whether hypertension and antihypertensive medication have anadverse effect on lung function in a general adult population.Methods: Within the population-based KORA F4 study 1319 adults aged 40-65 years performed lung function testsand blood pressure measurements. Additionally, information on anthropometric measurements, medical historyand use of antihypertensive medication was available. Multivariable regression models were applied to study theassociation between blood pressure, antihypertensive medication and lung function.Results: High blood pressure as well as antihypertensive medication were associated with lower forced expiratoryvolume in one second (p = 0.02 respectively p = 0.05; R2: 0.65) and forced vital capacity values (p = 0.01respectively p = 0.05, R2: 0.73). Furthermore, a detailed analysis of antihypertensive medication pointed out thatonly the use of beta-blockers was associated with reduced lung function, whereas other antihypertensivemedication had no effect on lung function. The adverse effect of beta-blockers was significant for forced vitalcapacity (p = 0.04; R2: 0.65), while the association with forced expiratory volume in one second showed a trendtoward significance (p = 0.07; R2: 0.73). In the same model high blood pressure was associated with reducedforced vital capacity (p = 0.01) and forced expiratory volume in one second (p = 0.03) values, too.Conclusion: Our analysis indicates that both high blood pressure and the use of beta-blockers, but not the use ofother antihypertensive medication, are associated with reduced lung function in a general adult population.BackgroundHypertension is an increasingly important public healthchallenge worldwide and it is one of the major causesfor morbidity and mortality [1]. Thus, the National HighBlood Pressure Education Program reports that the glo-bal burden of hypertension is approximately 1 billionindividuals and that more than 7 million deaths per yearmay be attributable to hypertension [2].Moreover, hypertension has been linked to multipleother diseases including cardiac, cerebrovascular, renaland eye diseases [3]. Beside the well-established associa-tion between hypertension and vascular comorbidities,several studies showed that blood pressure and lung func-tion are associated [4-9]. It could be demonstrated thathigher forced vital capacity (FVC) is a negative predictorof developing hypertension [7,8]. Moreover, some studiesfound an association between reduced pulmonary func-tion, including both low FVC and low forced expiratoryvolume in one second (FEV1), and hypertension [5,9,6].Furthermore,thereareanumber of publications dis-cussing the controversial Blood Flow and Blood Pressure Regulation Blood Flow and Blood Pressure Regulation Bởi: OpenStaxCollege Blood pressure (BP) is the pressure exerted by blood on the walls of a blood vessel that helps to push blood through the body Systolic blood pressure measures the amount of pressure that blood exerts on vessels while the heart is beating The optimal systolic blood pressure is 120 mmHg Diastolic blood pressure measures the pressure in the vessels between heartbeats The optimal diastolic blood pressure is 80 mmHg Many factors can affect blood pressure, such as hormones, stress, exercise, eating, sitting, and standing Blood flow through the body is regulated by the size of blood vessels, by the action of smooth muscle, by one-way valves, and by the fluid pressure of the blood itself How Blood Flows Through the Body Blood is pushed through the body by the action of the pumping heart With each rhythmic pump, blood is pushed under high pressure and velocity away from the heart, initially along the main artery, the aorta In the aorta, the blood travels at 30 cm/sec As blood moves into the arteries, arterioles, and ultimately to the capillary beds, the rate of movement slows dramatically to about 0.026 cm/sec, one-thousand times slower than the rate of movement in the aorta While the diameter of each individual arteriole and capillary is far narrower than the diameter of the aorta, and according to the law of continuity, fluid should travel faster through a narrower diameter tube, the rate is actually slower due to the overall diameter of all the combined capillaries being far greater than the diameter of the individual aorta The slow rate of travel through the capillary beds, which reach almost every cell in the body, assists with gas and nutrient exchange and also promotes the diffusion of fluid into the interstitial space After the blood has passed through the capillary beds to the venules, veins, and finally to the main venae cavae, the rate of flow increases again but is still much slower than the initial rate in the aorta Blood primarily moves in the veins by the rhythmic movement of smooth muscle in the vessel wall and by the action of the skeletal muscle as the body moves Because most veins must move blood against the pull of gravity, blood is prevented from flowing backward in the veins by one-way 1/6 Blood Flow and Blood Pressure Regulation valves Because skeletal muscle contraction aids in venous blood flow, it is important to get up and move frequently after long periods of sitting so that blood will not pool in the extremities Blood flow through the capillary beds is regulated depending on the body’s needs and is directed by nerve and hormone signals For example, after a large meal, most of the blood is diverted to the stomach by vasodilation of vessels of the digestive system and vasoconstriction of other vessels During exercise, blood is diverted to the skeletal muscles through vasodilation while blood to the digestive system would be lessened through vasoconstriction The blood entering some capillary beds is controlled by small muscles, called precapillary sphincters, illustrated in [link] If the sphincters are open, the blood will flow into the associated branches of the capillary blood If all of the sphincters are closed, then the blood will flow directly from the arteriole to the venule through the thoroughfare channel (see [link]) These muscles allow the body to precisely control when capillary beds receive blood flow At any given moment only about 5-10% of our capillary beds actually have blood flowing through them Art Connection (a) Precapillary sphincters are rings of smooth muscle that regulate the flow of blood through capillaries; they help control the location of blood flow to where it is needed (b) Valves in the veins prevent blood from moving backward (credit a: modification of work by NCI) Varicose veins are veins that become enlarged because the valves no longer close properly, allowing blood to flow backward Varicose veins are often most prominent on the legs Why you think this is the case? Link to Learning Visit this site to see the circulatory system’s blood flow 2/6 Blood Flow and Blood Pressure Regulation Proteins and other large solutes cannot leave the capillaries The loss of the watery plasma creates a hyperosmotic solution within the capillaries, especially near the venules This causes about 85% of the plasma that leaves the capillaries to eventually diffuses back into the capillaries near the venules The remaining 15% of blood plasma drains out from the interstitial fluid into nearby lymphatic vessels ([link]) The fluid in the lymph is similar in composition to the interstitial fluid The lymph fluid passes through lymph nodes before it returns to the heart via the vena cava Lymph nodes are specialized organs that filter the lymph by percolation through a maze of connective tissue filled with white blood cells The white blood cells remove infectious agents, such as bacteria ...Int. J. Med. Sci. 2011, 8 http://www.medsci.org 295 IInntteerrnnaattiioonnaall JJoouurrnnaall ooff MMeeddiiccaall SScciieenncceess 2011; 8(4):295-301 Research Paper Effects of p-Synephrine alone and in Combination with Selected Bioflavo-noids on Resting Metabolism, Blood Pressure, Heart Rate and Self-Reported Mood Changes Sidney J. Stohs1, Harry G Preuss2, Samuel C. Keith3, Patti L. Keith3, Howard Miller4, Gilbert R. Kaats3 1. Dean Emeritus, Creighton University Health Sciences Center, Omaha, NE 68178, USA 2. Department of Physiology, Georgetown University Medical Center, Washington, DC, USA 3. Integrative Health Technologies, Inc., 4940 Broadway, San Antonio, TX 78209, USA 4. Nutratech Inc., West Caldwell, NJ 07006, USA Corresponding author: Harry G. Preuss, M.D., preusshg@georgetown.edu, phone: 1-202-687-1441 © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/ licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2011.02.02; Accepted: 2011.03.06; Published: 2011.04.28 Abstract Bitter orange (Citrus aurantium) extract is widely used in dietary supplements for weight management and sports performance. Its primary protoalkaloid is p-synephrine. Most studies involving bitter orange extract and p-synephrine have used products with multiple ingredients. The current study assessed the thermogenic effects of p-synephrine alone and in conjunction with the flavonoids naringin and hesperidin in a double-blinded, randomized, place-bo-controlled protocol with 10 subjects per treatment group. Resting metabolic rates (RMR), blood pressure, heart rates and a self-reported rating scale were determined at baseline and 75 min after oral ingestion of the test products in V-8 juice. A decrease of 30 kcal occurred in the placebo control relative to baseline. The group receiving p-synephrine (50 mg) alone exhibited a 65 kcal increase in RMR as compared to the placebo group. The consumption of 600 mg naringin with 50 mg p-synephrine resulted in a 129 kcal increase in RMR relative to the placebo group. In the group receiving 100 mg hesperidin in addition to the 50 mg p-synephrine plus 600 mg naringin, the RMR increased by 183 kcal, an increase that was statistically sig-nificant with respect to the placebo control (p<0.02). However, consuming 1000 mg hes-peridin with 50 mg p-synephrine plus 600 mg naringin resulted in a RMR that was only 79 kcal greater than the placebo group. None of the treatment groups exhibited changes in heart rate or blood pressure relative to the control group, nor there were no differences in self-reported ratings of 10 symptoms between the treatment groups and the control group. This unusual finding of a thermogenic combination of ingredients that elevated metabolic rates without corresponding elevations in blood pressure and heart-rates warrants longer term studies to assess its value as a weight control agent. Key words: p-Synephrine, naringin, hesperidin, resting metabolic rate, heart rate, blood pressure Introduction The bioflavonoids hesperetin and naringenin are widely distributed in citrus fruits and juices as their glycosides, hesperidin and naringin, Int. J. Med. Sci. 2011, 8 http://www.medsci.org 192 IInntteerrnnaattiioonnaall JJoouurrnnaall ooff MMeeddiiccaall SScciieenncceess 2011; 8(3):192-197 Research Paper Effect of Acute Administration of an Herbal Preparation on Blood Pressure and Heart Rate in Humans John G. Seifert1, Aaron Nelson2, Julia Devonish2, Edmund R. Burke3, and Sidney J. Stohs4 1. Movement Science/Human Performance Laboratory, Montana State University, Bozeman, MT, USA 2. Human Performance Laboratory, St. Cloud State University, St. Cloud, MN, USA 3. Dept of Biology, Colorado University – Colorado Springs, Colorado Springs, CO, USA 4. School of Pharmacy and Health Professions, Creighton University Medical Center, Omaha, NE, USA Corresponding author: john.seifert@montana.edu, 406-994-7154 © Ivyspring International Publisher. This is an open-access article distributed under the terms of the Creative Commons License (http://creativecommons.org/ licenses/by-nc-nd/3.0/). Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. Received: 2010.10.05; Accepted: 2011.01.31; Published: 2011.03.02 Abstract Confusion and controversy exist regarding the cardiovascular effects of dietary supplements containing caffeine and Citrus aurantium (bitter orange) extract. The primary protoalkaloidal ingredient in bitter orange extract is p-synephrine which has some structural similarities to ephedrine and nor-epinehrine, but exhibits markedly different pharmacokinetic and receptor binding properties. The goal of this study was to investigate the cardiovascular effects of a product containing caffeine, bitter orange extract (p-synephrine) and green tea extract in mildly overweight individuals. Fourteen female and nine male subjects (age 24.7 +7.4 yrs, BMI: 26.6 +3.8) volunteered in this randomized, placebo-controlled, crossover, double-blind de-signed study. On day one, subjects entered the laboratory following an overnight fast. Heart rate and blood pressure were recorded at 60 min. Expired air was analyzed for the next 10 min of the session. At each of three meals, subjects ingested one capsule that was either a non-caloric placebo or a dietary supplement that contained 13 mg p-synephrine and 176 mg caffeine. On the following day, the subjects returned and repeated the protocol for data collection beginning 60 min after consuming one capsule of the placebo or the dietary sup-plement. No effects of the dietary supplement on heart rate, systolic and diastolic blood pressure or mean arterial pressure were observed. No between or within group differences were observed when data were analyzed for gender and caffeine usage. A small but significant decrease in resting respiratory exchange ratio was observed for the low caffeine user group in response to the product containing caffeine and p-synephrine. The results of this study in-dicate that ingestion of a product containing bitter orange extract, caffeine and green tea extract does not lead to increased cardiovascular stress and that fat oxidation may increase in certain populations. Key words: Citrus aurantium, p-synephrine, blood pressure, heart rate, bitter orange, caffeine, green tea Introduction Approximately two-thirds of the adult American population are overweight while about one-third is by definition considered to be obese [1]. The increase in obesity is associated with increased incidences of di-abetes, hypertension, hyperlipidemias, [...]... Moroyama-machi, Iruma-gun, Saitama 35 0-0 495 (Japan) Tel ϩ81 492 761611, Fax ϩ81 492 957338, E-Mail iromichi@saitama-med.ac.jp An Overview of Blood Pressure Regulation Associated with the Kidney 15 Suzuki H, Saruta T (eds): Kidney and Blood Pressure Regulation Contrib Nephrol Basel, Karger, 2004, vol 143, pp 16–31 Salt, Blood Pressure, and Kidney Toshiro Fujita, Katsuyuki Ando Department of Nephrology and Endocrinology,... ox-LDL receptor in endothelial cells has been focused A novel endothelial ox-LDL receptor, lectin-like ox-LDL receptor-1 (LOX-1) [26], has been considered to mediate ox-LDL-induced endothelial dysfunction, possibly through the upregulation of monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1 expression Since LOX-1 expression is upregulated by the mechanical stress, shear and stretch... media may contribute to the preserved baroreceptor sensitivity Dahl Salt-Sensitive Rats In Dahl salt-sensitive (DS) rats, elevation of blood pressure has been shown to result from salt loading and renal transplantation from DS rats to Dahl salt-resistant (DR) rats is able to elevate the recipient’s blood pressure In DS rats, the pressure- natriuresis relationship is blunted compared to that of DR rats... compared the pressure- natriuresis response curves of SHR and WistarKyoto (WKY) rats The pressure- natriuresis relationship curve in SHR was shifted toward higher pressure in comparison to WKY rats The inhibition of intrarenal RAS by MK-422 (ACE inhibitor) in SHR resulted in the excretion of more sodium at a given pressure, whereas no significant changes were observed An Overview of Blood Pressure Regulation. .. prostaglandins, dopamine, endogenous digitalis-like substance(s), endothelium-derived relaxing factor (nitric oxide), adrenomedullin, etc., could shift the curve to the right and/ or decrease its slope Thus, the mechanisms of salt-induced hypertension in Salt, Blood Pressure, and Kidney 19 30 0 pϽ 0.05 ⌬CO (%) pϽ 0.01 10 ⌬TPR (%) pϽ 0.01 20 Ϫ10 pϽ0.01 Ϫ20 Ϫ30 0 Salt-sensitive Non-salt-sensitive Salt-sensitive... circulatory volume To delineate the role of kidney in the control mechanism of blood pressure, we describe three major mechanisms that are involved, namely, renal blood flow (RBF), sympathetic nerve system, and pressure- natriuresis control (illustrated in figure 1) Blood pressure regulation in the kidney involves the interplay of these factors RBF receives 25% of cardiac output and the normal kidney adjusts... Na ϩK Kidney SHR pϽ0.05 Control p Ͻ0.05 Na Na ϩK Hypothalamus Fig 7 Decline in endogenous norepinephrine (NE) in kidney and hypothalamus to cold exposure in sodium (Na) and/ or potassium (K) loaded spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) Tissue NE was measured cold exposure (4ЊC) and 6 h after ␣-methyl-p-tyrosine (␣-MPT) administration Salt loading enhanced them markedly and. .. intraglomerular pressure High incidence of microalbuminuria High incidence of non-dippers Abnormal vascular endothelial function High incidence of cardiovascular events HDL ϭ high-density Physiology Cardiac Output, Blood Flow, and Blood Pressure ww.cambodiamed.com Cardiac Output Cardiac Output (CO) Is volume of blood pumped/min by each ventricle Heart Rate (HR) = 70 beats/min Stroke volume (SV) = blood pumped/beat by each ventricle ◦ Average is 70-80 ml/beat CO = SV x HR Total blood volume is about 5.5L ww.cambodiamed.com 14-4 Regulation of Cardiac Rate • Without neuronal influences, SA node will drive heart at rate of its spontaneous activity • Normally Symp & Parasymp activity influence HR (chronotropic effect) • Mechanisms that affect HR: chronotropic effect • Positive increases; negative decreases • Autonomic innervation of SA node is main controller of HR • Symp & Parasymp nerve fibers modify rate of spontaneous depolarization 14-5 Regulation of Cardiac Rate continued • NE & Epi stimulate opening of pacemaker HCN channels Fig 14.1 • This depolarizes SA faster, increasing HR • ACh promotes opening of K+ channels • The resultant K+ outflow counters Na+ influx, slows depolarization & decreasing HR 14-6 Regulation of Cardiac Rate continued • Vagus nerve: • Decrease activity: increases heart rate • Increased activity: slows heart • Cardiac control center of medulla coordinates activity of autonomic innervation • Sympathetic endings in atria & ventricles can stimulate increased strength of contraction 14-7 14-8 Stroke Volume • Is determined by variables: • End diastolic volume (EDV) = volume of blood in ventricles at end of diastole • Total peripheral resistance (TPR) = impedance to blood flow in arteries • Contractility = strength of ventricular contraction 14-9 Regulation of Stroke Volume • EDV is workload (preload) on heart prior to contraction • SV is directly proportional to preload & contractility • Strength of contraction varies directly with EDV • Total peripheral resistance = afterload which impedes ejection from ventricle • SV is inversely proportional to TPR • Ejection fraction is SV/ EDV (~80ml/130ml=62%) • Normally is 60%; useful clinical diagnostic tool 14-10 Frank-Starling Law of the Heart • States that strength of ventricular contraction varies directly with EDV Fig 14.2 • Is an intrinsic property of myocardium • As EDV increases, myocardium is stretched more, causing greater contraction & SV 14-11 Atrial Stretch Receptors • Are activated by increased venous return & act to reduce BP • Stimulate reflex tachycardia (slow HR) • Inhibit ADH release & promote secretion of ANP 14-58 Measurement of Blood Pressure • Is via auscultation (to examine by listening) • No sound is heard during laminar flow (normal, quiet, smooth blood flow) • Korotkoff sounds can be heard when sphygmomanometer cuff pressure is greater than diastolic but lower than systolic pressure • Cuff constricts artery creating turbulent flow & noise as blood passes constriction during systole & is blocked during diastole • 1st Korotkoff sound is heard at pressure that blood is 1st able to pass thru cuff; last occurs when can no long hear systole because cuff pressure = diastolic pressure 14-59 Measurement of Blood Pressure continued • Blood pressure cuff is inflated above systolic pressure, occluding artery • As cuff pressure is lowered, blood flows only when systolic pressure is above cuff pressure, producing Korotkoff sounds • Sounds are heard until cuff pressure equals diastolic pressure, causing sounds to disappear Fig 14.29 14-60 Fig 14.30 14-61 Pulse Pressure • Pulse pressure = (systolic pressure) – (diastolic pressure) • Mean arterial pressure (MAP) represents average arterial pressure during cardiac cycle • Has to be approximated because period of diastole is longer than period of systole • MAP = diastolic pressure + 1/3 pulse pressure 14-62 Hypertension 14-63 Hypertension • Is blood pressure in excess of normal range for age & gender (> 140/90 mmHg) • Afflicts about 20 % of adults • Primary or essential hypertension is caused by complex & poorly understood processes • Secondary hypertension is caused by known disease ... to blood flow is called peripheral resistance 4/6 Blood Flow and Blood Pressure Regulation Blood pressure is related to the blood velocity in the arteries and arterioles In the capillaries and. .. [link] Blood in the legs is farthest away from the heart and has to flow up to reach it Review Questions High blood pressure would be a result of 5/6 Blood Flow and Blood Pressure Regulation. . .Blood Flow and Blood Pressure Regulation valves Because skeletal muscle contraction aids in venous blood flow, it is important to get up and move frequently after long