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

Chronic administration of NG-nitro-L-arginine methyl ester (L-NAME) induces a rise in blood pressure that is prevented by angiotensin I-converting enzyme inhibitors or angiotensin II receptor (type 1) blockade. Alterations in vascular reactivity in this model have not been extensively studied and could potentially be involved in the pathogenesis of L-NAME-induced hypertension. In the present work, we aimed to study the vascular reactivity and cGMP content of aortic ring segments isolated from Wistar rats treated for 3 weeks with L-NAME or L-NAME plus the converting enzyme inhibitor quinapril. Quinapril prevented the rise in blood pressure in L-NAME-treated rats although acetylcholine-induced dilation in aortic rings was suppressed and sodium nitroprusside-induced dilation was increased in both L-NAME- and L-NAME plus quinapril-treated rats. In isolated aortic ring segments, chronic L-NAME decreased the contractile response to K+ (125 mmol/L), phenylephrine, angiotensin II, the G protein stimulator AlF4-, and the protein kinase C activator phorbol dibutyrate. In contrast to the upregulated sodium nitroprusside-induced dilation, the contractile capacity of the aorta in response to angiotensin II, phenylephrine, AlF4-, K+, and phorbol dibutyrate was restored by quinapril. Aortic cGMP was lowered in rats treated with L-NAME (530 +/- 120 fmol/mg protein, n = 12, P < .05) and L-NAME plus quinapril (461 +/- 140 fmol/mg protein, n = 12, P < .05) compared with controls (1798 +/- 522 fmol/mg protein, n = 12). We hypothesize that the continuous nitric oxide blockade by L-NAME might attenuate a continuous endogenous relaxing tone and is associated with an upregulated endogenous vasoconstrictor tone in large arteries. Converting enzyme inhibition interfered more with the increased endogenous constrictor tone than with the decreased vasodilator tone in the wall of large arteries from L-NAME-treated rats.
Hypertension 1996 Sep
PMID:In vitro alteration of aortic vascular reactivity in hypertension induced by chronic NG-nitro-L-arginine methyl ester. 879 17

Bradykinin is a mediator of the protection of myocardium by angiotensin I-converting enzyme/kininase II inhibitors. We reported that the activation of B2 bradykinin receptors in neonatal rat cardiac myocytes in primary culture was followed by hydrolysis of phosphatidylinositol 4,5-bisphosphate and formation of inositol 1,4,5-trisphosphate (IP3). Here we examine the regulation of IP3 formation stimulated by bradykinin. Activation of myocytes with 1 mu/L bradykinin increased IP3 production from 117 +/- 8.3 to 1011 +/- 48.6 pmol/mg protein. Treatment of the cells with 10 mu/L indomethacin or 1 mu/L dexamethasone partially blocked this bradykinin-induced response. Moreover, either U73122, a phospholipase C inhibitor, or (p-amylcinnamoyl) anthranilic acid, a phospholipase A2 inhibitor, blunted the IP3 response to bradykinin. Because thromboxane A2 stimulates inositol bisphosphate metabolism in guinea pig atria, we also investigated the effect of the thromboxane A2 receptor antagonist BM 13177 (1 mu/L), which strongly attenuated the stimulated IP3 production. Since thromboxane A2 appears to partly mediate the IP3 response to bradykinin, we examined the effect of the stable thromboxane A2 mimetic U46619. Control cultures were stimulated more by U46619 than by bradykinin (1629 +/- 14.5 versus 1011 +/- 48.6 pmol IP3/mg protein). This property of U46619 was selectively antagonized by BM 13177. Inhibition of either phospholipase C or phospholipase A2 blunted the IP3 response to U46619. Short-term (30 minutes) activation of protein kinase C with phorbol 12-myristate 13-acetate (10 pmol/L to 1 mu/L) attenuated the IP3 accumulation in response to bradykinin; the effect of phorbol 12-myristate 13-acetate was reversed with 1 mu/L staurosporine, a protein kinase C inhibitor. Treatment with 1 microgram/mL cholera toxin or pertussis toxin for 4 hours amplified the IP3 response to 10 nmol/L bradykinin from 570 +/- 20.0 to 1150 +/- 51.3 and to 1016.7 +/- 21.9 pmol/mg protein. Bradykinin mobilized 9.4% of intracellular calcium stores in cardiomyocytes as assessed by chlortetracycline-based fluorometry, and this effect of bradykinin was blocked by BM 13177 or the B2 bradykinin receptor blocker Hoe 140 by more than 70%. In functional studies, bradykinin (1 mu/L) increased by 12% the twitch contractile force of neonatal rat ventricular strips paced at threshold intensity, but this was unaffected by BM 13177. In conclusion, in cardiomyocytes, bradykinin enhances IP3 production mostly via phospholipase A2 stimulation and thromboxane A2 formation. This prostanoid in turn stimulates its receptor and activates phospholipase C, which then splits phosphatidylinositol 4,5-bisphosphate into IP3 and diacylglycerol. The effect of bradykinin on phospholipase C, via thromboxane A2, is negatively regulated by protein kinase C activation.
Hypertension 1996 Sep
PMID:Thromboxane A2 mediates the stimulation of inositol 1,4,5-trisphosphate production and intracellular calcium mobilization by bradykinin in neonatal rat ventricular cardiomyocytes. 879 31

Results from genetic investigations of blood pressure and other variables in inbred rodent models are reviewed here to illustrate the power of quantitative approaches for the detection of linkage and the ultimate identification of the underlying genes. Different studies-involving angiotensinogen and hypertension, angiotensin I-converting enzyme and cardiovascular diseases, and other traits-are used to illustrate the possibility of similar approaches to multifactorial disorders in humans.
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PMID:Quantitative phenotype analysis for localization and identification of disease-related genes in a complex genetic background. 882 79

The combination of single oral doses of an angiotensin I-converting enzyme inhibitor (captopril) and a type 1 angiotensin II receptor antagonist (losartan) has additive effects on blood pressure fall and renin release in sodium-depleted normotensive subjects. We planned the present study to determine whether the magnitude of the hemodynamic and hormonal consequences of renin-angiotensin system blockade by such a combination is larger than that obtained by doubling the dose of the angiotensin-converting enzyme inhibitor given alone. In a single-dose, double-blind, randomized, three-way crossover study, 10 mg enalapril, 20 mg enalapril, and the combination of 50 mg losartan and 10 mg enalapril were administered orally to 12 sodium-depleted normotensive subjects. The area under the time curve from 0 to 24 hours (AUC0-24) of the mean blood pressure fall after losartan-enalapril combination intake (-220 +/- 91 mm Hg.h) was significantly greater than that of either 10 or 20 mg enalapril (-124 +/- 91 and -149 +/- 85 mm Hg.h, respectively, P < .05 vs both doses). The combination significantly increased by 2.3 +/- 1.2-fold the AUC0-24 of plasma active renin compared with either 10 or 20 mg enalapril given alone (P < .05) but had no additive effect on plasma aldosterone fall. The losartan-enalapril combination is more effective in decreasing blood pressure and increasing plasma active renin than doubling of the enalapril dose.
Hypertension 1997 Feb
PMID:Additive effects of losartan and enalapril on blood pressure and plasma active renin. 904 Apr 50

The spontaneously hypertensive fawn-hooded rat (FHH) develops accelerated albuminuria and focal glomerular sclerosis (FGS), leading to ESRD and shortening of lifespan. The FHH is characterized by moderate systemic hypertension, a relatively low afferent to efferent arteriolar resistance ratio, and glomerular hypertension. The FHH study presented here was designed to examine the efficacy of early-onset, late-onset, or early-temporary angiotensin I-converting enzyme inhibition (ACE-i) in ameliorating long-term hypertension and FGS, and improving survival, as well as to relate its protective efficacy to preexistent FGS and to reduction of glomerular pressure (PGC) Untreated rats developed hypertension and high PGC, and all (N = 22) except one died of ESRD within the 72-wk follow-up period. Early-onset (at 7 wk of age) ACE-i prevented development of systemic and glomerular hypertension, and it largely prevented proteinuria and FGS; all rats survived throughout the follow-up period. Rats treated with late-onset (22 wk) ACE-i were hypertensive and proteinuric at the start of ACE-i, and they showed beginning FGS. ACE-i corrected the hypertension, albuminuria, and PGC but could not fully prevent some hypertension, albuminuria, and FGS at the later stage. Early-temporary (7 to 22 wk) ACE-i adequately controlled blood pressure and development of FGS during therapy, but after withdrawal of ACE-i, systemic and glomerular hypertension developed as in untreated animals. This regimen postponed but did not control FGS development and early mortality. The results of this study indicate that: (1) early-onset ACE-i very effectively protects against development of renal damage in the FHH; (2) this protection is associated with normalization of the elevated glomerular capillary pressure; (3) ACE-i cannot completely prevent further development of previously established FGS, despite lowering glomerular capillary pressure; (4) early-temporary ACE-i has no long-term controlling effect on arterial and glomerular pressure, and it cannot control development of FGS.
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PMID:Angiotensin-converting enzyme inhibition in the prevention and treatment of chronic renal damage in the hypertensive fawn-hooded rat. 904 44

We studied the expression of each component of the renin-angiotensin system (renin, angiotensin I-converting enzyme, angiotensinogen, and angiotensin II type I receptor) in balloon-injured rat carotid artery. We assessed the expression levels of the respective mRNAs by competitive polymerase chain reaction. Renin mRNA concentration was markedly increased 24 hours after balloon injury and remained higher than that in the control at 7 days after balloon injury. Angiotensin-converting enzyme mRNA concentration was decreased 24 hours after balloon injury and was increased at 14 days after balloon injury. No significant change in angiotensinogen mRNA concentration was observed throughout the study period. Angiotensin type I receptor mRNA concentration was increased beginning 3 days after balloon injury and remained higher than that in the control at 14 days after balloon injury. Immunohistochemical analysis showed that renin was transiently expressed in medial smooth muscle cells after balloon injury. Administration of quinapril markedly reduced neointimal formation and was accompanied by an attenuation of the increase in the concentrations of angiotensin type I receptor and angiotensin-converting enzyme mRNAs. The upregulation of renin mRNA in balloon-injured rat carotid artery preceded and may play a role in neointimal formation.
Hypertension 1997 Apr
PMID:Induction of renin in medial smooth muscle cells by balloon injury. 909 97

Previous observations on the heterogeneous distribution of von Willebrand factor in the vascular endothelium led us to examine the expression of angiotensin I-converting enzyme (ACE) in function of the vascular origin of endothelial cells (EC). EC from pig thoracic aorta, pulmonary artery, inferior vena cava and brain capillaries were cultured and assayed for ACE by enzymatic radiochemical determination and by western-blot and immunofluorescence using an antiACE polyclonal antibody. EC from the various vascular levels secreted ACE in the culture medium; western-blot analysis showed its presence at cellular level and immunofluorescence confirmed its location on the plasma membrane. But quantification revealed that EC from pulmonary artery contain more ACE than EC from the other vessels, especially from brain capillaries; immunofluorescence correlated well with the functional data. In contrast, secretion of ACE by brain capillaries EC was faster than that of arteries and of vena cava, the latter being the less effective. This differential ACE expression along the vascular tree could have a pharmacological implication since ACE inhibitors, used in the treatment of arterial hypertension, may act more at the vascular level than on the plasma renin-angiotensin system. On the other hand, endothelial distribution of ACE was different from that of von Willebrand factor; in particular we showed that EC cultured from vessels of pigs homozygous for the von Willebrand disease, in which von Willebrand factor synthesis was completely abolished, normally express ACE.
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PMID:Vascular origin determines angiotensin I-converting enzyme expression in endothelial cells. 914 23

Alterations in the structure of resistance and conduit arteries are a characteristic hallmark in hypertension. Studies carried out in hypertensive rats and in humans suggest that angiotensin I-converting enzyme inhibition has an effect on arterial structure of resistance arteries. In hypertensive rats the reduction of the media to lumen ratio is dose-dependent and significantly different from the effects of other antihypertensive agents at doses causing an equal degree of blood pressure reduction. In large conduit arteries, hypertrophy of the vessels is reversed by converting enzyme inhibition both in hypertensive rats (studies on central arteries) and in human (studies on peripheral arteries) hypertension. The reduction of hypertrophy is associated with a decrease in arterial stiffness, partly independent of blood pressure reduction. These findings suggest that regression of structural vascular changes may contribute to both the decrease in the arteriolar resistance and the improvement in the buffering function of large arteries. The decrease in arteriolar resistance and the improvement of large artery compliance may participate in blood pressure reduction and an improvement in pulse pressure amplification produced by converting enzyme inhibition.
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PMID:Resistance and conduit arteries following converting enzyme inhibition in hypertension. 916 39

Several studies have demonstrated the effectiveness of angiotensin I-converting enzyme (ACE) inhibitors in preventing the neointima formation found after denudation of the rat carotid artery by balloon injury. The aim of the present study was to determine the role of ACE in this model and to compare the treatment with the ACE inhibitor ramiprilat with that with the angiotensin II antagonist HR 720. The endothelial layer of the left carotid artery was removed using an inflated balloon catheter. Injured and control vessels were both submitted to histomorphological analysis and DNA content quantification at 2, 4, 6, 8, 12, and 14 days after injury. Evaluation of neointima thickening demonstrated a slow but steady increase of neointima that was significant after day 6 and reached 30% of the lumen in 2 weeks. This was paralleled by an increase in DNA content, which was significant 4 days after injury. ACE mRNA levels were quantified by polymerase chain reaction after reverse transcription. Measurement of ACE mRNA levels revealed a significant upregulation 2 and 8 days after injury, with no significant difference when compared with control tissue at later time points. ACE activity was also significantly enhanced at 2 and 8 days after injury, with no significant difference when compared with control tissue at later time points. In addition, the treatment with ramiprilat was more efficient in reducing neointima formation than that with HR 720. These data underlie the role of ACE in this model of restenosis. The early induction of ACE expression after endothelial injury but before significant changes in the vessel structure suggests that ACE activity might be one of the mechanisms that trigger neointima formation in the rat.
Hypertension 1997 Aug
PMID:Early induction of angiotensin I-converting enzyme in rat carotid artery after balloon injury. 926 Sep 92

An insertion/deletion (I/D) polymorphism of the angiotensin I-converting enzyme (ACE) gene has been identified that determines most of the plasma ACE activity genetically. Association of the D allele with insulin sensitivity and of the D/D genotype with coronary heart disease (CHD) has been reported in various ethnic populations. To study the role of this genetic polymorphism in patients with hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and NIDDM with CHD in a Taiwanese population, we used a polymerase chain reaction (PCR)-based genotyping technique with an insertion-specific primer for confirmation of the I allele. One hundred ninety-seven unrelated normal controls, 67 subjects with hypertension, 107 subjects with NIDDM, and 70 subjects with NIDDM and CHD were recruited for this study; all were Han Chinese. Subjects without a history of diabetes were studied by a standard 75-g oral glucose tolerance test. Hypertension was diagnosed according to the Fifth Joint National Committee criteria, and CHD was confirmed by a history of acute myocardial infarction and coronary angiographic intervention. The frequency of the I allele of the ACE gene in the normal population was 64.2%, which was higher than reported in white populations. The prevalence of the I allele of the ACE gene was not significantly increased in subjects with hypertension (73.1%), NIDDM (62.1%), and NIDDM with CHD (65%) compared with healthy controls. The I allele of the ACE gene did not correlate with demographic and metabolic variables. I/D polymorphism of the ACE gene is not a marker for hypertension, NIDDM, or CHD in this Taiwanese population.
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PMID:Insertion/deletion polymorphism of the angiotensin I-converting enzyme gene in patients with hypertension, non-insulin-dependent diabetes mellitus, and coronary heart disease in Taiwan. 932 9


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