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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac remodeling, which typically results from chronic hypertension or following an acute myocardial infarction, is a major risk factor for the development of heart failure and, ultimately, death. The renin-angiotensin system (RAS) has previously been established to play an important role in the progression of cardiac remodeling, and inhibition of a hyperactive RAS provides protection from cardiac remodeling and subsequent heart failure. Our previous studies have demonstrated that overexpression of angiotensin-converting enzyme 2 (ACE2) prevents cardiac remodeling and hypertrophy during chronic infusion of angiotensin II (ANG II). This, coupled with the knowledge that ACE2 is a key enzyme in the formation of ANG-(1-7), led us to hypothesize that chronic infusion of ANG-(1-7) would prevent cardiac remodeling induced by chronic infusion of ANG II. Infusion of ANG II into adult Sprague-Dawley rats resulted in significantly increased blood pressure, myocyte hypertrophy, and midmyocardial interstitial fibrosis. Coinfusion of ANG-(1-7) resulted in significant attenuations of myocyte hypertrophy and interstitial fibrosis, without significant effects on blood pressure. In a subgroup of animals also administered [d-Ala(7)]-ANG-(1-7) (A779), an antagonist to the reported receptor for ANG-(1-7), there was a tendency to attenuate the antiremodeling effects of ANG-(1-7). Chronic infusion of ANG II, with or without coinfusion of ANG-(1-7), had no effect on ANG II type 1 or type 2 receptor binding in cardiac tissue. Together, these findings indicate an antiremodeling role for ANG-(1-7) in cardiac tissue, which is not mediated through modulation of blood pressure or altered cardiac angiotensin receptor populations and may be at least partially mediated through an ANG-(1-7) receptor.
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PMID:Prevention of angiotensin II-induced cardiac remodeling by angiotensin-(1-7). 1709 28

The recent identification of angiotensin-converting enzyme 2 (ACE2) and Mas receptor opened new recognition of renin-angiotensin system (RAS). ACE2, a homologue of angiotensin-converting enzyme (ACE) generates angiotensin 1-7 directly through cleaving angiotensin II, or indirectly through angiotensin I in the body. Ang 1-7 exhibits vasodilatory and antiproliferative effects, and these effects were mainly mediated by Mas receptor. So ACE2-angiotensin1-7- Mas axis was considered a negative regulation in renin angiotensin system (RAS), and its significance has been implicated into hypertension and other cardiovascular diseases. The identification of the axis opens a new potential venue for further study and understanding of RAS.
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PMID:[Effects of ACE2-Ang 1-7-Mas axis on blood vessel]. 1743 52

Cardiac remodelling is a key risk factor for the development of heart failure in the chronic phase following myocardial infarction. Our previous studies have shown an anti-remodelling role of ACE2 (angiotensin-converting enzyme 2) in vivo during hypertension and that these protective effects are mediated through increased circulating levels of Ang-(1-7) [angiotensin-(1-7)]. In the present study, we have demonstrated that cardiac myocytes have modest ACE2 activity, whereas cardiac fibroblasts do not exhibit any endogenous activity. As fibroblasts are the major cell type found in an infarct zone following a myocardial infarction, we examined the effects of ACE2 gene delivery to cultured cardiac fibroblasts after acute hypoxic exposure. Cardiac fibroblasts from 5-day-old Sprague-Dawley rat hearts were grown to confluence and transduced with a lentiviral vector containing murine ACE2 cDNA under transcriptional control by the EF1alpha (elongation factor 1alpha) promoter (lenti-ACE2). Transduction of fibroblasts with lenti-ACE2 resulted in a viral dose-dependent increase in ACE2 activity. This was associated with a significant attenuation of both basal and hypoxia/re-oxygenation-induced collagen production by the fibroblasts. Cytokine production, specifically TGFbeta (transforming growth factor beta), by these cells was also significantly attenuated by ACE2 expression. Collectively, these results indicate that: (i) endogenous ACE2 activity is observed in cardiac myocytes, but not in cardiac fibroblasts; (ii) ACE2 overexpression in the cardiac fibroblast attenuates collagen production; and (iii) this prevention is probably mediated by decreased expression of cytokines. We conclude that ACE2 expression, limited to cardiac fibroblasts, may represent a novel paradigm for in vivo therapy following acute ischaemia.
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PMID:ACE2 overexpression inhibits hypoxia-induced collagen production by cardiac fibroblasts. 1760 May 30

Considering the importance of the renin-angiotensin system (RAS) for the central control of blood pressure and that nicotine increases the probability of development of hypertension associated to genetic predisposition, our aims are (1) to determine RAS in cultured neurons and glia from the brainstem and hypothalamus of spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats; (2) to analyze the possibility of nicotine to interact with brain RAS; and (3) to hypothesize any contribution of nicotine and RAS to the development of neurogenic hypertension. This study demonstrated physiological differences in RAS between cultured neuronal and glial cells from the brainstem and hypothalamus of SHR and WKY neonate rats. Our study also featured evidences of direct modulation of the RAS by nicotine in neurons and glia of brainstem and hypothalamus, which seems to be differential between the two rat strains. Such modulation gives us a clue about the mechanisms possibly involved in the genesis of neurogenic hypertension in vivo, for example, increase in angiotensin II type 1 receptor binding and decrease in angiotensin-converting enzyme 2. In conclusion, we demonstrated that neuronal and glial RAS from the brainstem and hypothalamus of SHR differ from WKY rats and nicotine differentially modulates the brain RAS in SHR and WKY.
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PMID:Nicotine modulates the renin-angiotensin system of cultured neurons and glial cells from cardiovascular brain areas of Wistar Kyoto and spontaneously hypertensive rats. 1795 38

Experimental evidence indicates that angiotensin-converting enzyme 2 (ACE2), a homologue of human ACE, might negatively regulate the activated renin-angiotensin-aldosterone system (RAAS) and might function as a protective regulator in the pathogenesis of hypertension. However, association studies regarding ACE2 are sparse in the literature, with negative results in the majority of cases. Here we conducted an association study between 2 intronic polymorphisms (A1075G and G8790A) of the ACE2 gene and stage 2 hypertension in Han Chinese. We genotyped the 2 polymorphisms in 1494 subjects (808 stage 2 hypertensives and 686 normotensives) recruited from the Fangshan district (Beijing). Data were analyzed using chi(2) test, 1-way analysis of variance, and logistic regression where appropriate. The frequency of A1075G allele distribution in males differed significantly (P < 0.0001), whereas the genotype and allele distributions of G8790A polymorphism were similar, between stage 2 hypertensives and normotensives. Systolic blood pressure (SBP) differed significantly in females across both genotypes: SBP was significantly lower in subjects with the 1075AA and 8790GG genotypes, higher in the 1075GG (+13.65 mm Hg versus AA) and 8790AA (+13.36 mm Hg versus GG) genotypes, and intermediate in the 1075AG (+5.76 mm Hg versus AA) and 8790GA (+5.65 mm Hg versus GG) genotypes. Our data suggest that the polymorphism (A1075G) might be a risk factor-at least a marker-for stage 2 hypertension in males and that the 2 studied polymorphisms might be the indicators of systolic hypertension in females.
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PMID:Correlation of angiotensin-converting enzyme 2 gene polymorphisms with stage 2 hypertension in Han Chinese. 1802

The renin-angiotensin system is a far more complex enzymatic cascade than realized previously. Mounting evidence suggests sex-specific differences in the regulation of the renin-angiotensin system and arterial pressure. We examined the hemodynamic responses, angiotensin II receptor subtypes, and angiotensin-converting enzyme 2 gene expression levels after graded doses of angiotensin II in males and females. Mean arterial pressure was measured via telemetry in male and female rats in response to a 2-week infusion of vehicle, low-dose (50 ng/kg per minute SC) or high-dose (400 ng/kg per minute SC) angiotensin II. The effect of concurrent infusion of the angiotensin II type 2 receptor (AT(2)R) blocker (PD123319) was also examined. The arterial pressure response to high-dose angiotensin II was attenuated in females compared with males (24+/-8 mm Hg versus 42+/-5 mm Hg; P for the interaction between sex and treatment <0.002). Remarkably, low-dose angiotensin II decreased arterial pressure (11+/-4 mm Hg; P for the interaction between sex and treatment <0.02) at a dose that did not have an effect in males. This decrease in arterial pressure in females was abolished by AT(2)R blockade. Renal AT(2)R, angiotensin-converting enzyme 2, and left ventricular AT(2)R mRNA gene expressions were markedly greater in females than in males with a renal angiotensin II type 1a receptor:AT(2)R ratio of approximately 1 in females. Angiotensin II infusion did not affect renal AT(2)R mRNA expression but resulted in significantly less left ventricular mRNA expression. Renal angiotensin-converting enzyme 2 mRNA expression levels were greater in females than in males treated with high-dose angiotensin II (approximately 2.5 fold; P for the interaction between sex and treatment <0.05). In females, enhancement of the vasodilatory arm of the renin-angiotensin system, in particular, AT(2)R and angiotensin-converting enzyme 2 mRNA expression, may contribute to the sex-specific differences in response to renin-angiotensin system activation.
Hypertension 2008 Oct
PMID:Enhanced angiotensin II type 2 receptor mechanisms mediate decreases in arterial pressure attributable to chronic low-dose angiotensin II in female rats. 1893 41

Rat models of hypertension, eg, spontaneously hypertensive stroke-prone rats (SHRSP), display reduced angiotensin-converting enzyme 2 (ACE2) mRNA and protein expression compared with control animals. The aim of this study was to investigate the role of ACE2 in the pathogenesis of hypertension in these models. Therefore, we generated transgenic rats on a SHRSP genetic background expressing the human ACE2 in vascular smooth muscle cells by the use of the SM22 promoter, called SHRSP-ACE2. In these transgenic rats vascular smooth muscle expression of human ACE2 was confirmed by RNase protection, real-time RT-PCR, and ACE2 activity assays. Transgene expression leads to significantly increased circulating levels of angiotensin-(1-7), a prominent product of ACE2. Mean arterial blood pressure was reduced in SHRSP-ACE2 compared to SHRSP rats, and the vasoconstrictive response to intraarterial administration of angiotensin II was attenuated. The latter effect was abolished by previous administration of an ACE2 inhibitor. To evaluate the endothelial function in vivo, endothelium-dependent and endothelium-independent agents such as acetylcholine and sodium nitroprusside, respectively, were applied to the descending thoracic aorta and blood pressure was monitored. Endothelial function turned out to be significantly improved in SHRSP-ACE2 rats compared to SHRSP. These data demonstrate that vascular ACE2 overexpression in SHRSP reduces hypertension probably by locally degrading angiotensin II and improving endothelial function. Thus, activation of the ACE2/angiotensin-(1-7) axis may be a novel therapeutic strategy in hypertension.
Hypertension 2008 Nov
PMID:Transgenic angiotensin-converting enzyme 2 overexpression in vessels of SHRSP rats reduces blood pressure and improves endothelial function. 1880 90

The High Blood Pressure Research Conference of the American Heart Association is a theoretical meeting for hypertension researchers who direct their attention to hypertension-related basic disease mechanisms. The items that I have selected for this brief review are molecular intracellular receptor function, novel angiotensin (Ang)-related pathways, including Ang-(1-7), the Mas receptor, and angiotensin-converting enzyme 2, oxidative stress, immunity, the (pro)renin receptor, and until now unappreciated signalling pathways, such as the tonicity element binding protein.
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PMID:Renin-angiotensin system-related highlights from the High Blood Pressure Research Conference annual meeting. 1912 66

Postural tachycardia syndrome (POTS) is associated with increased plasma angiotensin II (Ang II). Ang II administered in the presence of NO synthase inhibition with nitro-L-arginine (NLA) and Ang II type 1 receptor blockade with losartan produces vasodilation during local heating in controls. We tested whether this angiotensin-mediated vasodilation occurs in POTS and whether it is related to angiotensin-converting enzyme 2 (ACE2) and Ang-(1-7). We used local cutaneous heating to 42 degrees C and laser Doppler Flowmetry to assess NO-dependent conductance at 4 calf sites in 12 low-flow POTS and in 12 control subjects 17.6 to 25.5 years of age. We perfused Ringer's solution through intradermal microdialysis catheters and performed local heating. We perfused one catheter with NLA (10 mmol/L)+losartan (2 microg/L) and repeated heating, and NLA+losartan+Ang II (10 micromol/L), repeating heating a third time. A second catheter received NLA+losartan+Ang II, heated, perfused NLA+losartan+Ang II+DX600 (1 mmol/L; a selective ACE2 inhibitor), and reheated. A third catheter received NLA+losartan+Ang II, heated, perfused NLA+losartan+Ang II+Ang-(1-7) (100 micromol/L), and reheated. The fourth catheter received Ang-(1-7) then reheated a second time only. Angiotensin-mediated vasodilation was present in control but not POTS. Ang-mediated dilation was eliminated by DX600, indicating an ACE2-related effect. Ang-mediated vasodilation was restored in POTS by Ang-(1-7). When administered alone during locally mediated heating, Ang-(1-7) improved the NO-dependent local heating response. ACE2 effects are blunted in low-flow POTS and restored by the ACE2 product Ang-(1-7). Data imply impaired catabolism of Ang II through the ACE2 pathway. Vasoconstriction in POTS may result from a reduction in Ang-(1-7) and an increase in Ang II.
Hypertension 2009 May
PMID:Defects in cutaneous angiotensin-converting enzyme 2 and angiotensin-(1-7) production in postural tachycardia syndrome. 1928 53

The orphan transporter Slc6a18 (XT2) is highly expressed at the luminal membrane of kidney proximal tubules and displays approximately 50% identity with Slc6a19 (B(0)AT1), which is the main neutral amino acid transporter in both kidney and small intestine. As yet, the amino acid transport function of XT2 has only been experimentally supported by the urinary glycine loss observed in xt2 null mice. We report here that in Xenopus laevis oocytes, co-expressed ACE2 (angiotensin-converting enzyme 2) associates with XT2 and reveals its function as a Na(+)- and Cl(-)-de pend ent neutral amino acid transporter. In contrast to its association with ACE2 observed in Xenopus laevis oocytes, our experiments with ace2 and collectrin null mice demonstrate that in vivo it is Collectrin, a smaller homologue of ACE2, that is required for functional expression of XT2 in kidney. To assess the function of XT2 in vivo, we reanalyzed its knock-out mouse model after more than 10 generations of backcrossing into C57BL/6 background. In addition to the previously published glycinuria, we observed a urinary loss of several other amino acids, in particular beta-branched and small neutral ones. Using telemetry, we confirmed the previously described link of XT2 absence with hypertension but only in physically restrained animals. Taken together, our data indicate that the formerly orphan transporter XT2 functions as a sodium and chloride-de pend ent neutral amino acid transporter that we propose to rename B(0)AT3.
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PMID:Orphan transporter SLC6A18 is renal neutral amino acid transporter B0AT3. 1947 81


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