Drug treatment of hypertension: focus on vascular health

Hypertension, the most common preventable risk factor for cardiovascular disease and death, is a growing health burden. Serious cardiovascular complications result from target organ damage including cerebrovascular disease, heart failure, ischaemic heart disease and renal failure. While many systems contribute to blood pressure (BP) elevation, the vascular system is particularly important because vascular dysfunction is a cause and consequence of hypertension. Hypertension is characterised by a vascular phenotype of endothelial dysfunction, arterial remodelling, vascular inflammation and increased stiffness. Antihypertensive drugs that influence vascular changes associated with high BP have greater efficacy for reducing cardiovascular risk than drugs that reduce BP, but have little or no effect on the adverse vascular phenotype. Angiotensin converting enzyme ACE inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) improve endothelial function and prevent vascular remodelling. Calcium channel blockers also improve endothelial function, although to a lesser extent than ACEIs and ARBs. Mineralocorticoid receptor blockers improve endothelial function and reduce arterial stiffness, and have recently become more established as antihypertensive drugs. Lifestyle factors are essential in preventing the adverse vascular changes associated with high BP and reducing associated cardiovascular risk. Clinicians and scientists should incorporate these factors into treatment decisions for patients with high BP, as well as in the development of new antihypertensive drugs that promote vascular health

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

AbstractAging is an intricate process modulated by different molecular and cellular events, such as genome instability, epigenetic and transcriptional changes, molecular damage, cell death and senescence, inflammation, and metabolic dysfunction. Particularly, protein quality control (chaperone systems) tends to be negatively affected by aging, thus leading to cellular senescence in metabolic tissues and, as a consequence, to the increasing dissemination of inflammation throughout the body. The heat shock (HS) response and its associated expression of the 70 kDa family of heat shock proteins (HSP70), which are anti-inflammatory molecular chaperones, are found to be markedly decreased during muscle inactivity and aging, while evidence supports the loss of HSP70 as a key mechanism which may drive muscle atrophy, contractile dysfunction, and reduced regenerative capacity. In addition, abnormal stress response is linked with higher incidence of neurodegenerative diseases as well as low-grade inflammatory diseases that are associated with physical inactivity and obesity. Therefore, strategies to increase or, at least, to maintain the levels of HSP70, and its accompanying HS response to stress, are key to reduce biological cell dysfunctions that occur in aging. In this sense, physical exercise is of note as it is the most powerful inducer of the HS response, comparable only to heat stress and fever-like conditions. On the other hand, the amino acid l-glutamine, whose production within the skeletal muscle and liberation into the blood stream is dependent on muscle activity, is a potentializer of HSP70 expression and HS response, particularly via its entering in hexosamine biosynthetic pathway (HBP). Herein, we discuss the collaborative role of glutamine (and its donors/precursors) and physical exercise (mostly responsible for glutamine release into the circulation) as potential tools to increase HSP70 expression and the HS response in the elderly.</jats:p

Pharmacologic approaches against advanced glycation end products (ages) in diabetic cardiovascular disease

Advanced Glycation End-Products (AGEs) are signaling proteins associated to several vascular and neurological complications in diabetic and non-diabetic patients. AGEs proved to be a marker of negative outcome in both diabetes management and surgical procedures in these patients. The reported role of AGEs prompted the development of pharmacological inhibitors of their effects, giving rise to a number of both preclinical and clinical studies. Clinical trials with anti-AGEs drugs have been gradually developed and this review aimed to summarize most relevant reports

Effect of Different Types of Physical Activity on Activities of Daily Living in Older Adults : Systematic Review and Meta-Analysis

Peer reviewedPostprin

Tjelesna neaktivnost je uzrok, a tjelesna aktivnost lijek za glavne javnozdravstvene probleme

Uvod Čvrsti znanstveni dokazi pokazuju da su mnoge bolesti ili prekursori bolesti češći u osoba koje se rijetko ili uopće ne bave tjelesnom aktivnošću nego kod redovito fizički aktivnih osoba. Broj bolesti ili stanja koje potiče tjelesna neaktivnost posljednjih je desetljeća kontinuirano rastao. Tjelesna je aktivnost bila i ostaje neizostavan biološki podražaj nužan za održavanje struktura i funkcija organa i organskih sustava. Većina, ako ne i sve adaptacijske promjene, uzrokovane umjerenom učestalošću i intenzitetom tjelesne aktivnosti, djeluju tako da poboljšavaju zdravlje, unapređujući strukturu i/ ili funkcionalnu sposobnost odgovarajućeg organa. Mnoge adaptacijske promjene također smanjuju rizik od određenih bolesti ili prekursora bolesti, npr. prekomjerne tjelesne mase ili pretilosti. Tjelesna neaktivnost, pak, kao nedostatak biološkog podražaja, ima sasvim suprotne učinke i povećava rizik od čitavog niza bolesti. Tjelesna neaktivnost u narušavanju zdravlja Atrofija mišića, gubitak jakosti i snage. Sarkopenija, gubitak mišićne mase, jakosti i funkcije povezan sa starenjem, dovodi do slabljenja tjelesne funkcije, povećava rizik od padova, ubrzava gubitak koštane mase i time povećava rizik od osteoporoze. Nedostatak tjelesne aktivnosti bitan je čimbenik pojačanja i ubrzanja razvoja sarkopenije. Osteoporoza i osteoporotični prijelomi. Tjelesna neaktivnost može utjecati na rizik od osteoporotičnih prijeloma povećavanjem rizika razvoja osteoporoze i rizika od padova. Osteoartritis. Tjelesna neaktivnost je izravno i neizravno povezana s razvojem i rizikom razvoja osteoartritisa. Križobolja. Između 70 i 85% ljudi tijekom života iskusi simptome boli, mišićne napetosti i ukočenosti križne i lumbalne regije leđa. U osoba s križoboljom tjelesna neaktivnost pogoršava simptome. Prekomjerna težina i pretilost. Povećanjem rizika za nastanak pretilosti, kao i povećanjem negativnih posljedica pretilosti, osobito metaboličkih promjena, tjelesna neaktivnost uvelike utječe na negativan zdravstveni učinak pretilosti. Diabetes mellitus tipa 2. Niz prospektivnih studija dokazao je da tjelesna neaktivnost povećava rizik za razvoj dijabetesa tipa 2 za 20 do 70%. Hipertenzija. Niska razina opće psihofizičkog dobrog stanja ili pripremljenosti (fitnesa) povezana je s oko 50% većim rizikom za razvoj hipertenzije. Metabolički sindrom. Smatra se da osoba ima metabolički sindrom ako se u nje modu dijagnosticirati ili više sljedećih simptoma: visok krvni tlak, povišena razina glukoze u krvi, povišena razina triglicerida u plazmi, nizak kolesterol HDL, povećan opseg struka. Važnost tjelesne neaktivnosti u patofiziologiji metaboličkog sindroma proizlazi iz središnje uloge skeletnih mišića u metabolizmu ugljikohidrata i masti. Koronarna bolest srca. Rizik od koronarne bolesti srca je 30 do 50% veći u tjelesno neaktivnih nego u barem umjereno aktivnih osoba. Cerebrovaskularna bolest (moždani udar). Brojne studije ukazuju na ulogu tjelesne neaktivnosti kao rizičnog faktora moždanog udara. Periferna vaskularna bolest. Tjelesna neaktivnost važan je čimbenik za razvoj ateroskleroze, čime utječe i na razvoj periferne vaskularne bolesti. Rak. Pokazatelji o povezanosti tjelesne neaktivnosti sa 30 do 40% većim rizikom od nastanka karcinoma debelog crijeva vrlo su čvrsti. Nešto manje dosljedni, no ipak dovoljni dokazi pokazuju da tjelesna neaktivnost u pred- i postmenopauzalnih žena povećava rizik od raka dojke za 20 do 30%. Postoje i donekle ograničeni pokazatelji o povezanosti tjelesne neaktivnosti i povećanog rizika za nastanak raka endometrija i prostate. Ukupna smrtnost. Desecima znanstvenih istraživanja utvrđeno je da tjelesna neaktivnost povećava rizik ukupne smrtnosti populacije, s najvećim udjelom smrtnosti od kardiovaskularnih bolesti. Tjelesna aktivnost kao protulijek za negativne posljedice tjelesne neaktivnosti Spektar tjelesnih aktivnosti koje pozitivno utječu na zdravlje kreće se od općenitih, individualnih aktivnosti u svrhu poboljšanja zdravlja do vrlo specijaliziranih, specifičnih, stručno planiranih i nadziranih medicinskih programa vježbanja. Mišićna masa, jakost i snaga, sarkopenija. Tjelesna aktivnost koja održava i povećava mišićnu masu i jakost ključna je komponenta za poboljšanje zdravlja, osobito u starijoj populaciji. Koštana masa, osteoporoza i rizik od fraktura. Zbog povećanja ili održavanja koštane mase i čvrstoće te smanjenja rizika od padova, tjelesna aktivnost predstavlja važan čimbenik u prevenciji osteoporoze i osteoporotičnih prijeloma. Zglobovi i artritis. Svojim utjecajem na zglobnu hrskavicu i okolne strukture, osobito mišiće, tjelesna aktivnost povoljno utječe na sam zglob. Križobolja. Rezultati kontroliranih studija pokazuju da redovita umjerena tjelovježba može spriječiti nastanak križobolje. Vratobolja. Istraživanja pokazuju da tjelovježba koja uključuje jačanje vratnih mišića učinkovito ublažuje tegobe uzrokovane kroničnim bolovima vrata. Prekomjerna težina i pretilost. Povećanjem potrošnje energije, a time i održanjem energetske ravnoteže, tjelesna aktivnost igra važnu ulogu u prevenciji pretilosti. Dijabetes tipa 2. Porast tjelesne aktivnosti smanjuje rizik za nastanak dijabetesa tipa 2. Izgleda da je taj učinak povezan s količinom aktivnosti. Hipertenzija. Pojačana tjelesna aktivnost ima znatne zdravstveno pozitivne učinke vezane uz povišen krvni tlak i njegove posljedice. Metabolički sindrom. Vježbe aerobnog tipa učinkovite su u ublažavanju i otklanjanju različitih komponenata metaboličkog sindroma u pretile djece i odraslih. Koronarna bolest srca. Trenutno vrijedi preporuka o bavljenju aerobnim oblicima tjelovježbe umjerenog intenziteta barem 30 minuta većinu dana u tjednu. Preporuka je dijelom donesena na temelju saznanja o učinkovitosti tjelesne aktivnosti u prevenciji koronarne bolesti srca. Kronično zatajenje srca (insuficijencija). Tjelovježba se preporuča kao dio cjelokupne njege pacijenata sa zatajenjem srca. Cerebrovaskularna bolest (moždani udar). Tjelesna aktivnost učinkovita je mjera u prevenciji moždanog udara. Periferna arterijska bolest (Claudicatio intermittens). Tjelovježba, pogotovo nadgledano pješačenje, vrlo je učinkovita u liječenju i sekundarnoj prevenciji ove bolesti. Duljina ho-danja bez nastupa bolova prosječno se produžava za 150%. Rak. Trenutačno nije poznato u kojoj bi točno mjeri tjelesna aktivnost mogla umanjiti rizik od određenih vrsta zloćudnih bolesti, kao ni koja bi “doza” tjelesne aktivnosti za to bila odgovarajuća. Najrazboritija je preporuka o redovitoj tjelesnoj aktivnosti umjerenog intenziteta nekoliko puta tjedno, svaki put u trajanju od najmanje pola sata. Slabljenje kognitivnih sposobnosti povezano sa starenjem. Tjelovježba se može smatrati i oblikom “gimnastike za mozak”, oso-bito ako je raznovrsna te ako zahtijeva i razvija motoričke vještine. Zaključna poruka Trenutna znanstvena saznanja uvjerljivo pokazuju da tjelesna neaktivnost, koja je u različitom stupnju prisutna u najvećem dijelu populacije većine svjetskih zemalja, predstavlja ozbiljnu opasnost za zdravlje, funkcionalnu sposobnost i kvalitetu života. Taj se negativan utjecaj pojačava neodgovarajućom prehranom i drugim faktorima povezanima s prevladavajućim načinom (sedentarnim) života u industrijaliziranim zemljama, a sve više i u zemljama u tranziciji, ali i u zemljama u razvoju. Iako pravi lijek za negativne učinke tjelesne neaktivnosti (antidot), tjelesna aktivnost još uvijek, nažalost, uvelike pripada privatnoj, individualnoj sferi. Ipak, na društvu je i državi odgovornost da pruži prave informacije o važnosti redovite tjelovježbe te da osigura uvjete i proširi mogućnosti za sigurno bavljenje raznim tjelesnim aktivnostima

The effect of different training modes on skeletal muscle microvascular density and endothelial enzymes controlling NO availability

It is becoming increasingly apparent that a high vasodilator response of the skeletal muscle microvasculature to insulin and exercise is of critical importance for adequate muscle perfusion and long-term microvascular and muscle metabolic health. Previous research has shown that a sedentary lifestyle, obesity, and ageing lead to impairments in the vasodilator response, while a physically active lifestyle keeps both microvascular density and vasodilator response high. To investigate the molecular mechanisms behind these impairments and the benefits of exercise training interventions, our laboratory has recently developed quantitative immunofluorescence microscopy methods to measure protein content of eNOS and NAD(P)Hoxidase specifically in the endothelial layer of capillaries and arterioles of human skeletal muscle. As eNOS produces NO and NAD(P)Hoxidase superoxide anions (quenching NO) we propose that the eNOS/NAD(P)Hoxidase protein ratio is a marker of vasodilator capacity. The novel methods show that endurance training (ET) and high intensity interval training (HIT) generally regarded as a time efficient alternative to ET, increase eNOS protein content and the eNOS/NADP(H) oxidase protein ratio in previously sedentary lean and obese young men. Resistance exercise training had smaller but qualitatively similar effects. Western blot data of other laboratories suggest that endurance exercise training leads to similar changes in sedentary elderly men. Future research will be required to investigate the relative importance of other sources and tissues in the balance between NO and O2- production seen by the vascular smooth muscle layer of terminal arterioles

The application of whole-body vibration in physiotherapy – A narrative review

Whole-body vibration (WBV) training is a very popular kind of practice in sport, fitness and physiotherapy. This work reviews the current knowledge regarding the use and effectiveness of WBV in the physiotherapy. The discrepancies between different authors’ results are probably due to divergence in WBV training protocols. The paperwork clearly showed that despite its ultimate effects, exercises on a vibration platform are safe, feasible, and well tolerated by patients with different disorders. This narrative review should help physiotherapists verify therapy programs regarding patients’ exposure to WBV

Resistance training and co-supplementation with creatine and protein in older subjects with frailty: a small-scale exploratory study

This is a small-scale exploratory trial from the Pro-Elderly study (“Protein Intake and Resistance Training in Aging”) aimed at gathering knowledge on the feasibility, efficacy and safety of co-supplementation with creatine and protein supplementation, in conjunction with resistance training, in older individuals with frailty. Methods: A 14-week, double-blind, randomized, parallel-group, placebo controlled exploratory trial was conducted between in Hamilton (New Zealand). The subjects were randomly assigned to compose either one of the following groups: 1) whey protein and creatine co-supplementation (WHEY+CR) or 2) whey protein supplementation (WHEY). All the subjects undertook a supervised exercise training program for 14 weeks and were assessed at baseline and after 14 weeks. The main dependent variables were muscle function (handgrip, timed-stands and timed-up-and go tests) and body composition (free fat mass, fat mass, and bone mass). Self-reported adverse events were recorded throughout the trial and blood parameters were assessed. Results: We found a main time-effect in handgrip (WHEY+CR = 26.65 ± 31.29; WHEY = 13.84 ± 14.93 Kg; p = 0.0005), timed-up-and-go (WHEY+CR = 11.20 ± 9.37; WHEY = -17.76 ± 21.74; p = 0.006 s), and timed-stands-test (WHEY+CR = 47.50 ± 35.54; WHEY = 46.87 ± 24.23 reps; p = 0.0001), suggesting that WHEY+CR and WHEY were similarly effective in improving muscle function. Exploratory analyses further suggested that most of the subjects experienced improvements in all muscle function tests. In addition, all of the subjects showed improvements in at least two of the three tests, regardless of their treatments. Neither within- nor between-group differences were detected in any of the body composition variables (all p > 0.05). No important adverse effect was observed and blood parameters remained unaltered. Conclusion: Co-supplementation with creatine and whey protein was tolerable and free of adverse events in older subjects with frailty undertaking resistance training. Furthermore creatine supplementation did not augment the adaptive effects of resistance training along with whey protein on body composition or muscle function in this population. Resistance training and co-supplementation with creatine and protein in older subjects with frailty iii This exploratory study will be insightful in designing a larger and more comprehensive randomized controlled trial to confirm or refute these findings. Clinicaltrials.gov: NCT0189038