Effects of One Resistance Exercise Session on Vascular Smooth Muscle of Hypertensive Rats / Efeitos de uma Sessão de Exercício Resistido sobre o Músculo Liso Vascular de Ratos Hipertensos

AbstractBackground:Hypertension is a public health problem and increases the incidence of cardiovascular diseases.Objective:To evaluate the effects of a resistance exercise session on the contractile and relaxing mechanisms of vascular smooth muscle in mesenteric arteries of NG-nitro L-arginine methyl ester (L-NAME)-induced hypertensive rats.Methods:Wistar rats were divided into three groups: control (C), hypertensive (H), and exercised hypertensive (EH). Hypertension was induced by administration of 20 mg/kg of L-NAME for 7 days prior to experimental protocols. The resistance exercise protocol consisted of 10 sets of 10 repetitions and intensity of 40% of one repetition maximum. The reactivity of vascular smooth muscle was evaluated by concentration‑response curves to phenylephrine (PHEN), potassium chloride (KCl) and sodium nitroprusside (SNP).Results:Rats treated with L-NAME showed an increase (p < 0.001) in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) compared to the initial period of induction. No difference in PHEN sensitivity was observed between groups H and EH. Acute resistance exercise reduced (p < 0.001) the contractile response induced by KCl at concentrations of 40 and 60 mM in group EH. Greater (p < 0.01) smooth muscle sensitivity to NPS was observed in group EH as compared to group H.Conclusion:One resistance exercise session reduces the contractile response induced by KCl in addition to increasing the sensitivity of smooth muscle to NO in mesenteric arteries of hypertensive rats.

ResumoFundamento:A hipertensão é um problema de saúde pública e faz aumentar a incidência das doenças cardiovasculares.Objetivo:Avaliar os efeitos de uma sessão de exercício resistido sobre os mecanismos contráteis e relaxantes do músculo liso vascular em artéria mesentérica de ratos hipertensos induzidos por L-NAME.Métodos:Ratos Wistar foram divididos em três grupos: Controle (C), Hipertenso (H) e Hipertenso Exercitado (HE). A hipertensão foi induzida pela administração de 20 mg/kg de NG-nitro L-arginina metil éster (L-NAME) durante sete dias antes dos protocolos experimentais. O protocolo de exercício resistido consistiu em dez séries de dez repetições e intensidade de 40% de uma repetição máxima. A reatividade do músculo liso vascular foi avaliada através de curvas concentração-resposta para a fenilefrina (FEN), cloreto de potássio (KCl) e nitroprussiato de sódio (NPS).Resultados:Os ratos tratados com L-NAME apresentaram aumento (p < 0,001) da Pressão Arterial Sistólica (PAS), da Pressão Arterial Diastólica (PAD) e da Pressão Arterial Média (PAM) quando comparados ao período inicial da indução. Não foi observada diferença na sensibilidade da FEN entre os grupos H e HE. O exercício resistido agudo reduziu (p < 0,001) a resposta contrátil induzida pelo KCl nas concentrações de 40 e 60 mM do grupo HE quando comparado ao grupo H. Foi observado maior (p < 0,01) sensibilidade do músculo liso ao NPS no grupo HE quando comparado ao grupo H.Conclusão:Uma sessão de exercício resistido reduz as respostas contráteis induzidas pelo KCl, além de aumentar a sensibilidade do músculo liso ao NO em artéria mesentérica de ratos hipertensos.

Inhibition of PKC-dependent extracellular Ca2+ entry contributes to the depression of contractile activity in long-term pressure-overloaded endothelium-denuded rat aortas

We examined the contractile responsiveness of rat thoracic aortas under pressure overload after long-term suprarenal abdominal aortic coarctation (lt-Srac). Endothelium-dependent angiotensin II (ANG II) type 2 receptor (AT2R)-mediated depression of contractions to ANG II has been reported in short-term (1 week) pressure-overloaded rat aortas. Contractility was evaluated in the aortic rings of rats subjected to lt-Srac or sham surgery (Sham) for 8 weeks. ANG I and II levels and AT2R protein expression in the aortas of lt-Srac and Sham rats were also evaluated. lt-Srac attenuated the contractions of ANG II and phenylephrine in the aortas in an endothelium-independent manner. However, lt-Srac did not influence the transient contractions induced in endothelium-denuded aortic rings by ANG II, phenylephrine, or caffeine in Ca2+-free medium or the subsequent tonic constrictions induced by the addition of Ca2+ in the absence of agonists. Thus, the contractions induced by Ca2+ release from intracellular stores and Ca2+ influx through stored-operated channels were not inhibited in the aortas of lt-Srac rats. Potassium-elicited contractions in endothelium-denuded aortic rings of lt-Srac rats remained unaltered compared with control tissues. Consequently, the contractile depression observed in aortic tissues of lt-Srac rats cannot be explained by direct inhibition of voltage-operated Ca2+ channels. Interestingly, 12-O-tetradecanoylphorbol-13-acetate-induced contractions in endothelium-denuded aortic rings of lt-Srac rats were depressed in the presence but not in the absence of extracellular Ca2+. Neither levels of angiotensins nor of AT2R were modified in the aortas after lt-Srac. The results suggest that, in rat thoracic aortas, lt-Srac selectively inhibited protein kinase C-mediated activation of contraction that is dependent on extracellular Ca2+ entry.

Myosin light chain kinase is necessary for post-shock mesenteric lymph drainage enhancement of vascular reactivity and calcium sensitivity in hemorrhagic-shocked rats

Vascular hyporeactivity is an important factor in irreversible shock, and post-shock mesenteric lymph (PSML) blockade improves vascular reactivity after hemorrhagic shock. This study explored the possible involvement of myosin light chain kinase (MLCK) in PSML-mediated vascular hyporeactivity and calcium desensitization. Rats were divided into sham (n=12), shock (n=18), and shock+drainage (n=18) groups. A hemorrhagic shock model (40±2 mmHg, 3 h) was established in the shock and shock+drainage groups. PSML drainage was performed from 1 to 3 h from start of hypotension in shock+drainage rats. Levels of phospho-MLCK (p-MLCK) were determined in superior mesenteric artery (SMA) tissue, and the vascular reactivity to norepinephrine (NE) and sensitivity to Ca2+ were observed in SMA rings in an isolated organ perfusion system. p-MLCK was significantly decreased in the shock group compared with the sham group, but increased in the shock+drainage group compared with the shock group. Substance P (1 nM), an agonist of MLCK, significantly elevated the decreased contractile response of SMA rings to both NE and Ca2+ at various concentrations. Maximum contractility (Emax) in the shock group increased with NE (from 0.179±0.038 to 0.440±0.177 g/mg, P<0.05) and Ca2+ (from 0.515±0.043 to 0.646±0.096 g/mg, P<0.05). ML-7 (0.1 nM), an inhibitor of MLCK, reduced the increased vascular response to NE and Ca2+ at various concentrations in the shock+drainage group (from 0.744±0.187 to 0.570±0.143 g/mg in Emax for NE and from 0.729±0.037 to 0.645±0.056 g/mg in Emax for Ca2+, P<0.05). We conclude that MLCK is an important contributor to PSML drainage, enhancing vascular reactivity and calcium sensitivity in rats with hemorrhagic shock.

Modulação redox da homeostase de células musculares lisas através de estimuladores do sistema NADPH oxidase / Redox modulation of smooth muscle cells homeostasis via inductors of NADPHoxidase system

As doenças cardiovasculares representam a principal causa de morte nos países ocidentais. Dentre essas doenças, a aterosclerose é que mais se destaca, sendo caracterizada pelo acúmulo de células musculares lisas vasculares (CMLV). O efeito patológico das CMLV em resposta a diferentes estímulos pode acarretar em disfunções nestas células. É notável que a aterosclerose ocorra principalmente em vasos sinuosos onde ocorre um forte turbilhonamento do fluxo sanguíneo, que pode acarretar em hemólise e, consequentemente, acúmulo de heme livre. Além disso, no processo de aterogênese as moléculas de adesão, principalmente integrinas, são de crucial importância durante a resposta de CMLV. Nesse trabalho nosso objetivo inicial foi avaliar o efeito do heme livre nas funções de CMLV, bem como os mecanismos moleculares por trás desses efeitos. Em uma segunda parte, investigamos o envolvimento da integrina α1ß1 no efeito da Angiotensina II (Ang II) em CMLV. Nós observamos que o heme livre é capaz de induzir a proliferação e migração de CMLV via espécies reativas de oxigênio (ERO) provenientes da NADPHoxidase (NADPHox). Adicionalmente vimos que o heme ativa vias de sinalização redox-sensíveis relacionadas à proliferação celular, como MAPKinases e o fator de transcrição NFκB. Também observamos que há uma ligação entre a NADPHox e o sistema heme oxigenase (HO), uma vez que o heme induz a expressão de HO-1 e o pré-tratamento das CMLV com inibidores de HO levam ao aumento tanto o efeito proliferação quanto a indução de ERO promovidas pelo heme. Além disso, vimos que o efeito contra-regulatório promovido pela HO ocorre devido as metabolites do heme: biliverdina, bilirrubina e monóxido de carbono. Por último, quando bloqueamos tanto a NADPHox quanto o sistema HO o heme não teve efeito algum na proliferação de CMLV...

Cardiovascular diseases represent the major mortality reason in western countries. Among these diseases, atherosclerosis is the most prominent one, which is characterized by vascular smooth muscle cell (VSMC) accumulation. The pathological effect of VSMC in response to different stimuli is able to induce VSMC dysfunctions. Notably, this cardiovascular disease occurs mainly in sinuous vessels with turbulent blood flow, which may lead to hemolysis and consequent free heme accumulation. Furthermore, in atherogenesis the adhesion molecule, mainly integrins, were of crucial importance during the VSMC response. In this work our aim was to elucidate the effect of free heme in VSMC, as well the molecular mechanisms underlying this process. In a second part, we investigated the role of α1ß1 integrin in Angiotensin II (Ang II) effect on VSMC. We observed that free heme is able to induce VSMC proliferation in a Reactive Oxygen Species (ROS) derived from NADPHoxidase (NADPHox) dependent manner. Additionally, heme activates proliferation-relationed redox-sensitive signaling routes, such as MAPKinases and the transcription factor NFκB. It was also observed a critical crosstalk between NADPHox and heme oxygenase (HO) system, once heme induces HO-1 expression and VSMC pretreatment with HO inhibitors increased heme proliferative effect and ROS production. Accordingly, we observed that the counter-regulatory effect promoted by HO occurs due heme metabolites: biliverdin, bilirubin and carbon monoxide. Finally, when both NADPHox and HO system were blocked, heme had no effect on VSMC proliferation...

New nitric oxide donors based on ruthenium complexes

Nitric oxide (NO) donors produce NO-related activity when applied to biological systems. Among its diverse functions, NO has been implicated in vascular smooth muscle relaxation. Despite the great importance of NO in biological systems, its pharmacological and physiological studies have been limited due to its high reactivity and short half-life. In this review we will focus on our recent investigations of nitrosyl ruthenium complexes as NO-delivery agents and their effects on vascular smooth muscle cell relaxation. The high affinity of ruthenium for NO is a marked feature of its chemistry. The main signaling pathway responsible for the vascular relaxation induced by NO involves the activation of soluble guanylyl-cyclase, with subsequent accumulation of cGMP and activation of cGMP-dependent protein kinase. This in turn can activate several proteins such as K+ channels as well as induce vasodilatation by a decrease in cytosolic Ca2+. Oxidative stress and associated oxidative damage are mediators of vascular damage in several cardiovascular diseases, including hypertension. The increased production of the superoxide anion (O2-) by the vascular wall has been observed in different animal models of hypertension. Vascular relaxation to the endogenous NO-related response or to NO released from NO deliverers is impaired in vessels from renal hypertensive (2K-1C) rats. A growing amount of evidence supports the possibility that increased NO inactivation by excess O2- may account for the decreased NO bioavailability and vascular dysfunction in hypertension.

Ondas ultra-sônicas de alta freqüência causam disfunção endotelial em artérias coronárias caninas epicárdicas / High-frequency ultrasonic waves cause endothelial dysfunction on canine epicardial coronary arteries

OBJETIVO: Aplicação de energia por ultra-som pode facilitar a remoção da placa ateromatosa, mas o efeito desse procedimento em vasos próximos ainda é matéria de estudos experimentais. MÉTODOS: Para determinar se a energia ultra-sônica compromete a produção de óxido nítrico, segmentos de artérias coronárias caninas foram expostos a baixos (0-10 W) e altos (25 W) níveis de energia por 15 segundos, utilizando-se protótipo de aparelho para a realização de endarterectomia. Após exposição, segmentos das artérias coronarianas foram estudados em organ chambers. Para os ensaios farmacológicos foram utilizadas as seguintes drogas:difosfato de adenosina (ADP), acetilcolina (Ach) e fluoreto de sódio (NaF) para a avaliação do relaxamento dependente do endotélio. O nitroprussiato de sódio (NPS) e o isoproterenol foram utilizados para a avaliação do relaxamento independente do endotélio. RESULTADOS: A aplicação de alta energia ultra-sônica comprometeu o relaxamento dependente do endotélio induzido por ADP (10-9 - 10-4 M), Ach (10-9 - 10-4 M) e NaF (0,5 -9,5 mM) em artérias coronarianas epicárdicas. Entretanto, baixos valores de energia ultra-sônica não alteraram o relaxamento dependente do endotélio (nem o relaxamento máximo e nem a EC50) induzido pelos mesmos agonistas. O relaxamento da musculatura lisa vascular induzido por isoproterenol (10-9 - 10-5 M) ou NPS (10-9 - 10-6 M) não foi comprometido, tanto por baixos, quanto por altos níveis de energia ultra-sônica. CONCLUSÃO: Os experimentos demonstram que altas energias ultra-sônicas alteram a função endotelial. Entretanto, o ultra-som não altera a habilidade de relaxamento da musculatura lisa vascular de artérias caninas epicárdicas.

OBJECTIVE: Application of ultrasound energy by an endarterectomy probe can facilitate the removal of atheromatous plaque, but the effect of this procedure on surrounding vessel structure and function is still a matter of experimental investigations. METHODS: To determine whether ultrasound energy impairs the production of nitric oxide or damages vascular smooth muscle function, isolated canine epicardial coronary artery segments were exposed to either high (25 W) or low (0-10 W) ultrasonic energy outputs, for 15 seconds, using an endarterectomy device prototype. After exposure, segments of epicardial coronary artery were studied in organ chambers. The following drugs were used: adenosine diphosphate (ADP), acetylcholine (Ach) and sodium fluoride (NaF) to study endothelium-dependent relaxation and sodium nitroprusside (SNP) and isoproterenol to evaluate endothelium-independent relaxation. RESULTS: Application of high ultrasonic energy power impaired endothelium-dependent relaxation to ADP (10-9 - 10-4 M), Ach (10-9 - 10-4 M) and NaF (0.5 - 9.5 mM) in epicardial coronary arteries. However, low ultrasound energy output at the tip of the probe did not alter the endothelium-dependent relaxation (either maximal relaxation or EC50) to the same agonists. Vascular smooth muscle relaxation to isoproterenol (10-9 - 10-5 M) or SNP (10-9 - 10-6 M) was unaltered following exposure to either low or high ultrasonic energy outputs. CONCLUSION: These experiments currently prove that ultrasonic energy changes endothelial function of epicardial coronary arteries at high power. However, ultrasound does not alter the ability of vascular smooth muscle of canine epicardial coronary arteries to relax.

Effects of acid-base imbalance on vascular reactivity

Acid-base homeostasis maintains systemic arterial pH within a narrow range. Whereas the normal range of pH for clinical laboratories is 7.35-7.45, in vivo pH is maintained within a much narrower range. In clinical and experimental settings, blood pH can vary in response to respiratory or renal impairment. This altered pH promotes changes in vascular smooth muscle tone with impact on circulation and blood pressure control. Changes in pH can be divided into those occurring in the extracellular space (pHo) and those occurring within the intracellular space (pHi), although, extracellular and intracellular compartments influence each other. Consistent with the multiple events involved in the changes in tone produced by altered pHo, including type of vascular bed, several factors and mechanisms, in addition to hydrogen ion concentration, have been suggested to be involved. The scientific literature has many reports concerning acid-base balance and endothelium function, but these concepts are not clear about acid-base disorders and their relations with the three known mechanisms of endothelium-dependent vascular reactivity: nitric oxide (NO/cGMP-dependent), prostacyclin (PGI2/cAMP-dependent) and hyperpolarization. During the last decades, many studies have been published and have given rise to confronting data on acid-base disorder and endothelial function. Therefore, the main proposal of this review is to provide a critical analysis of the state of art and incentivate researchers to develop more studies about these issues.

Mechanical factors of cardiovascular risk in systemic arterial hypertension: A new sign of arterial rigidity / Factores mecánicos de riesgo cardiovascular en la hipertensión arterial sistémica: Un nuevo signo de rigidez arterial

Antecedent: By means of sphygmokinetocardiography (SKCG) we developed and arterial rigidity index (ARI) which measure the pulse wave aortic carotid reflexion time over the left ventricular ejection time (LVET). This index, together with the pulse wave velocity (PWV) and the pulse pressure (PP) are indicators of arterial stiffness. In this paper we measured these index in 27 systemic artery hypertension. Cases (group A, GA), with and without left ventricular hypertrophy (subgroups: A1 SGA1, n = 13, and A2, SGA2, n = 14), respectively, and 28 normotensive cases (group B, GB). Protocol: In two occasions: after 3 minutes of sitting position (SP) and after 3 minute of jogging in an upright position (UP), blood pressure, ARI, PP, PWV (aortic-hand finger distance/aorto-hand finger pulse time) and R-IV interval (electrocardiographic R wave-left early ventricular kinetocardiography deflexion) were measured. Results: Demography was similar in GA and GB. Systolic, diastolic and pulse pressure were significantly higher in GA vs GB. LVET (ms) was lower in GA vs GB in SP (268 ± 42 vs 274 ± 40, p < 0.001, respectively) and higher postexercise UP (280 ± 42 vs 244 ± 46, p < 0.001). PWV m/s were higher in SP in GA vs GB (9.8 ± 2.8 vs 7.4 ± 1.2, p < 0.001, respectively) and in UP (10.1 ± 1.9 vs 7.9 ± 9, p < 0.001, respectively). ARI was lower in UP in GA vs GB (0.48 ± 0.3 vs 0.80 ± 0.3, p < 0.003). Correlation index of PP vs SBP, vs DBP and vs PWV were significant in SP and in UP. Height had a significant correlation vs ARI in SP and UP (r = 0.60, p < 0.01, and r = 0.42, p < 0.05, respectively). Conclusion: PWV is increased in GA vs GB patients. The ARI index is lower in GA vs GB cases in post exercise. PWV and PP showed a statistical significant correlation; height vs ARI had also a significant correlation: SKCG is a new method, that uses a not commercially instrument, which should have clinical application.

Antecedentes: Mediante esfigmoquinetocardiografía (EQCG) se desarrolló un índice de rigidez arterial (IRA) que mide el tiempo aorto-onda de reflexión arterial sobre el período expulsivo. Este índice junto con la velocidad de la onda del pulso (VOP) y la presión del pulso (PP) son signos de rigidez arterial. Aquí medimos estos indicadores en 27 casos con hipertensión arterial (grupo A, GA) con y sin hipertrofia del ventrículo izquierdo: subgrupo A1, SGA1 de 13 casos y 14 individuos (subgrupo A2, SGA2) respectivamente y 28 casos normotensos (grupo B, GB). Protocolo: En 2 ocasiones: después de 3 minutos de posición sedente (PS) y después de 3 minutos de trote en posición ortostática (PO), se midió: la presión arterial (PA), el IRA, la VOP (distancia aorta-dedo-mano/tiempo de la onda del pulso aorta-dedo-mano) la PP y el intervalo R-IV (onda R del electrocardiograma -final de la deflexión ventricular temprana en el EQCG. Resultados: La demografía fue similar en ambos grupos. La PP, las presiones sistólica y diastólica fueron más altas en el GA vs el GB. El PE (ms) fue menor en el GA vs el GB en PS (268 ± 42 vs 274 ± 40, p < 0.001, respect.) y más alto en PO (280 ± 42 vs 244 ± 46, p < 0.001) en el GA vs GB. La VOP m/s, fue más alta en PS en GA vs GB (9.8 ± 2.8 vs 7.4 ± 1.2, p < 0.001, respect.) y en PO (10.1 ± 1.9 vs 7.9 ± 9, p < 0.001, respect.). El IRA fue menor en PO en el GA vs GB (0.48 ± 0.3 vs 0.8 ± 0.3, p < 0.003). El índice de correlación de la PP vs PAS, PA y VOP tuvo significancia estadística en PS y en PO. La talla correlacionó con el IRA (r = 0.6, p < 0.01 en PS y r = 0.42, p < 0.05 en PO). Conclusiones: La VOP está aumentada y el IRA más bajo en el GA vs GB en PO (lo que indica mayor rigidez arterial). La VOP y la PP tuvieron correlación significativa con la talla al igual que esta última con el IRA. La EQCG es un método con aplicación clínica. (Arch Cardiol Mex 2003; 73:261-270).

Vascular Ó1D-Adrenoceptor function is maintained during congestive heart failure after myocardial infarction in the rat

Background. During congestive heart failure, desensitization of ß-adrenoceptors is related to a lower adrenergic responsiveness in the heart; little is known about Ó1D-adrenoceptors in the vasculature under this condition. We evaluated Ó1D-adrenoceptor response in aorta and carotid arteries in a model of congestive heart failure (CHF) post-myocardial infarction. Methods. Noradrenaline-elicited contraction was determined in endothelium-denuded arterial rigs from young (10-week-old) Wistar rats in the absence and presence of the Ó1D-adrenoceptor antagonist BMY 7378 (8-(2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl)-8-azaspiro(4,5)decane-7,9-dione dihydrochloride) in sham-operated rats and in rats that development CHF 4 weeks or 7 months after myocardial infarction. Results. In the thoracic aorta, BMY 7378 displaced noradrenaline affect to the right with PA2 values of: sham, 8.58 ñ 0.12; CHF, 8.36 ñ 0.13, and sham, 8.50 ñ 0.10; CHF, 7.99 ñ 0.13 at 4 weeks and 7 months after myocardial infarction, respectively. While in carotid arteries, the pA2 values were: sham, 8.43 ñ 0.19; CHF, 8,81 ñ 0.19, and sham, 8.35 ñ 0.18; CHF, 8,29 ñ 0.08 at 4 weeks and 7 months after myocardial infarction, respectively. Ehen adul (7-month-old) rats were subjected to myocardial infarction, CHF was not installed and pA2 values were similar and high in both sham and infarcted rats. Conclusions. These results indicate that Ó1D-adrenoceptors remained as the main receptors involved in contraction in aorta and carotid arteries, irrespective of CHF duration

Stress and atherogenesis: smooth muscle cell mitogenic activity and other biochemical changes associated with sera of stressed subjects

The proliferation of smooth muscle cells in the arterial wall [VSMC] is considered to play a key role in the development of atherosclerosis. To investigate the possible contribution of "stress" [experimentally induced] to this process, blood from healthy volunteers, ages 21 to 65, screened to exclude major risk factors for coronary heart disease, was assayed for mitogenic activity after the subjects were exposed to one of 2 "stress" conditions. These consisted of a cognitive task with superimposed verbal harassment [group 1], and the cognitive task without harassment [group 2]. Mitogenic activity was determined by studying the growth stimulatory effects of PDGF-depleted plasma derived serum [PDS] from "stressed" subjects added to cultured VSMC, as measured by incorporation of radioactive thymidine into DNA or increase in cell number. In addition, changes in the steady state of the mRNA for the c-myc protooncogene were also assayed in VSMC by Northern blot analysis, using sera showing the greatest differential "pre/post stress" mitogenic activity. Blood pressure [BP], heart rate [HR], cortisol, and serum total and HDL cholesterol were also evaluated. All measurements were made immediately before [baseline] and after a 30 min interval. Analysis of the data revealed that there were 33% of subjects in group 1 with an increase of thymidine incorporation 15% or greater than baseline, versus 21% in group 2. The average increases were 45% and 30%. A higher percentage [35-42%] of subjects in group 1 responded with increases in systolic and diastolic blood pressure, compared to subjects in group 2 [15-20%]; the average in blood pressure was 10-15%. Similarly, more subjects [52%] in group 1 had an elevated [average 10-15%] serum cortisol, compared to the 42% in group 2 subjects. HR, total HDL cholesterol showed slight changes only. These results suggest that psychoactive factors may affect cardiovascular systems via rapid elicited rises in serum mitogenic activity for VSMC

Las arterias pulmonares distales en los habitantes de las alturas / The pulmonary distal arteries at high altitude population

El estudio de las arterias pulmonares, en el hombre y en los animales que viven en las grandes alturas, ha demostrado la existencia de varios cambios morfológicos, como la muscularización de las arteriolas así como la proliferación de células musculares lisas en la íntima de las arterias distales. Estos cambios están relacionados con una vasoconstricción como respuesta a la hipoxia y al desarrollo de una hipertensión arterial pulmonar que, en algunos casos, se asocian con hipertrofia ventricular derecha e insuficiencia cardiaca congestiva, como en la enfermedad subaguda de la altura, descrita en el Himalaya y en los Andes en el hombre y en ciertas especies animales. Una posible pérdida de la respuesta vasoconstrictiva por transmisión genética a la hipoxia crónica se ha observado como una aclimatización o adaptación a las grandes alturas.