UMLS:C0020538 - FACTA Search

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

Ramipril, a converting enzyme inhibitor, was first studied in rats with aortic stenosis, an experimental model of reno-vascular hypertension. In this study, ramipril has an antihypertrophic cardiac effect, independently to its hypotensive effect. The co-administration of Hoe 140, a specific antagonist of bradykinin receptors blocked totally the effect of ramipril on blood pressure, cardiac hypertrophy and on concentration of cGMP. These effects can therefore be explained by an accumulation of bradykinins. Furthermore, we investigated the preventing effects of ramipril on left ventricular hypertrophy, on growth of cardiac capillaries using SHR rats, treated in utero and during the 20 weeks following birth with two doses: a relatively high dose (1 mg/kg/day) and a low dose (0.01 mg/kg/day). Animals treated with a low dose of ramipril presented a high blood pressure similar to that observed in the control group. At the end of the treatment, the converting enzyme activity was inhibited in both groups. An increase in the growth of cardiac capillaries and of the cardiac concentration of glycogen and a decrease in the cardiac concentration of citric acid was observed in both groups. The ventricular weight decreased only in the high dose treatment group. This results demonstrated that early treatment with converting enzyme inhibitor even with a low dose which was unable to prevent the development of hypertension and of left ventricular hypertrophy. We could therefore draw a hypothesis of an accumulation of bradykinin due to the converting enzyme inhibitor which could explain in part this effect through an improvement of cardiac metabolism.
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PMID:[Inhibition of the enzyme of conversion and cardioprotection: role of bradykinins]. 132 27

To evaluate the role of bradykinin in the antihypertrophic effect of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, we investigated the influence of HOE 140, a specific B2-receptor antagonist, on the effects of ramipril on left ventricular hypertrophy (LVH) in rats with aortic banding. Ramipril at a dose of 1 mg kg-1 day-1 for 6 weeks prevented the increase in blood pressure and development of LVH after aortic banding; plasma ACE activity was significantly inhibited. A lower dose of ramipril (10 micrograms kg-1 day-1 for 6 weeks) had no effect on the increase in blood pressure or on plasma ACE activity, but prevented LVH after aortic banding. The antihypertrophic effects of the higher and the lower dose ramipril, as well as the antihypertensive action of the higher dose of ramipril were abolished by the coadministration of HOE 140 (500 micrograms kg-1 day-1). The present data show for the first time that the beneficial effects of an ACE-inhibitor on LVH in rats with hypertension caused by aortic banding can be prevented by a specific B2-receptor antagonist.
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PMID:A specific B2-bradykinin receptor antagonist HOE 140 abolishes the antihypertrophic effect of ramipril. 132 47

Left ventricular hypertrophy (LVH) is a common condition and a powerful independent risk factor for coronary heart disease, congestive heart failure, and other cardiac morbidity. It is associated with the male sex and advancing age. Its most common cause is hypertension, and many antihypertensive agents induce regression of LVH. Angiotensin-converting enzyme (ACE) inhibitors have been shown to reverse LVH by a mechanism as yet unknown. Reduction in afterload and other hemodynamic abnormalities by reduction of blood pressure is clearly a factor, but ACE inhibitors also block adrenergic action and other sympathetic nervous system influences, and the reduction in angiotensin II produces many effects. By inhibiting this potent vasoconstrictor and suppressing its degradation of the powerful vasodilator bradykinin, and by promoting sodium and water excretion, ACE inhibitors contribute to the restoration of normal ventricular function. Angiotensin II promotes protein synthesis in myocardial myocytes, and blocking this action may arrest the hypertrophic process. To determine the effect of angiotensin II on LVH and normalization of LV function, a study is now underway evaluating the effects of lisinopril, a new lysine analog of enalapril, and a diuretic agent in the treatment of hypertension LVH.
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PMID:ACE inhibitors and regression of left ventricular hypertrophy. 132 1

The purpose of this study was to gain insight into the mechanism(s) responsible for the exaggerated angiotensin II (ANG II)-induced renal vasoconstriction during the development of hypertension. In previous studies we observed that ANG II produces a twofold larger decrease in renal blood flow (RBF) in spontaneously hypertensive (SHR) compared with Wistar-Kyoto (WKY) rats before but not after cyclooxygenase inhibition. We suggested that this strain difference could be attributed to differences in renal prostaglandin (PG) levels and/or action. To evaluate these possibilities, measurements of RBF were made in 6-wk-old, anesthetized SHR and WKY pretreated with indomethacin. ANG II was injected intrarenally before and during continuous intrarenal infusion of a low dose of PGE2, viprostol (PGE2 analogue), PGI2, iloprost (PGI2 analogue), and bradykinin. In the control period ANG II reduced RBF by 50% in both strains. Infusion of PGs reduced the vasoconstrictor effect of ANG II in WKY, but had no effect in SHR. In contrast, infusion of bradykinin blunted the ANG II-induced vasoconstriction to a similar degree in both WKY and SHR. To investigate whether this lack of protection in SHR is due to strain differences in the number and/or affinity of renal receptors of PGs, radiolabeled ligand binding studies for PGE2 and PGI2 receptors were undertaken in glomeruli isolated from young WKY and SHR. Scatchard analysis revealed a single, high-affinity receptor site for PGE2 that was similar in both strains of rats. Both strains also exhibited a single, high-affinity PGI2 receptor site. No differences were observed in the PGE2 or PGI2 receptor number between WKY and SHR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Impaired ability of prostaglandins to buffer renal vasoconstriction in genetically hypertensive rats. 132 56

The contribution of endogenous bradykinin to the chronic antihypertensive actions of the ACE-inhibitor, ramipril, was investigated in 2-kidney 1 clip (2K1C) hypertensive kinin-deficient Brown Norway Katholieke rats (BN-K) and 2K1C hypertensive Wistar rats (WI) as well as in spontaneously hypertensive rats (SHR). Treatment with ramipril plus the BK B2-receptor antagonist HOE 140 for 6 weeks significantly attenuated the antihypertensive effects of the ACE-inhibitor in 2K1C hypertensive WI rats, but not in 2K1C hypertensive BN-K rats and in SHR. Our data support the hypothesis that potentiation of endogenous kinins contributes to the chronic antihypertensive actions of ACE-inhibitors in experimental renal hypertension. Whether this holds also true for other forms of hypertension remains to be answered.
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PMID:Kinin contribution to chronic antihypertensive actions of ACE-inhibitors in hypertensive rats. 133 42

Combined hypertension treatment with inhibitors of the converting enzyme (ICE) and diuretocs gives manifold advantages, the most important of them is a synergistic action of both drugs resulting in blood pressure decrease and prevention of hypokaliaemia. The purpose of the present study was assessment of the effect of hydrochlorothiazide in 50 mg daily doses on blood levels of kininogen and prekallikrein and on plasma renin activity (PRA) in hypertensive patients treated during captopril 150 mg daily alone during 3 weeks, without success. The study was carried out on 15 patients with essential hypertension stage III after WHO. A control group comprised 18 healthy subjects. The determinations were done three time: before treatment, after 3 weeks on captopril, and after 2 weeks of combined treatment with captopril and hydrochlorothiazide. It was found combined treatment with captopril and hydrochlorothiazide produced blood pressure normalization in patients insufficiently responding to captopril alone. During the combined treatment normalization of blood pressure was associated with a higher fall of kininogen concentration, higher rise of prekallikrein and PRA in relation to the values obtained with captopril alone. This evidenced a more pronounced reaction of the kinin system and the renin-angiotensin-aldosterone system to the combined treatment as compared with the response of both systems to captopril alone.
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PMID:[Effect of hydrochlorothiazide on various components of the kinin system and plasma renin activity in patients with arterial hypertension treated with captopril]. 133 10

Two metallopeptidases, angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) are involved respectively in the release of angiotensin II which is a vasoconstrictor, and in the metabolism of atrial natriuretic peptide which is diuretic and bradykinin which is a vasodilatator. The dual inhibition of these two peptidases represents a new way to regulate the blood pressure in various cardiovascular diseases. Taking into account the mechanism of action of metallopeptidases and the substrate specificity of ACE and NEP, dual inhibitors corresponding to the general formula HS-CH2-CH(R1)CONH-CH(R2)COOH and HS-CH(R1)CONH-CH(R2)CONH-CH(R3)COOH and having inhibitory potencies on each enzyme in the nanomolar range were designed. The most efficient inhibitors have been transformed into lipophilic prodrugs which were found to be active after oral administration. These compounds have been tested on an experimental model of hypertension in rats and, as expected, have been shown to be both diuretic (NEP inhibition) and hypotensive (ACE inhibition).
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PMID:[Dual inhibition of converting enzyme and neutral endopeptidase: a research new way in the field of hypertension]. 133 91

1. The angiotensin converting enzyme (ACE) activity of spontaneously hypertensive (SHR) and spontaneously hypertensive stroke-prone (SHRSP) rats was compared to the ACE activity of normotensive Wistar-Kyoto rats (WKY). 2. ACE activity was assessed indirectly in conscious unrestrained rats using the equipressor response end point to simultaneously calculate the extent of conversion of angiotensin I (AI) to angiotensin II (AII) and the pulmonary degradation of bradykinin (BK). 3. The pulmonary degradation of BK was significantly elevated (99.4%) in SHR rats whereas the elevation was not significant in SHRSP rats (99.2%) compared to WKY rats, even though the pulmonary inactivation of BK in WKY rats was higher (98.6%) than in normotensive Wistar rats (95.6% and 97.5%) previously studied. 4. Blood pressure responsiveness to intra-aortically injected BK (bolus injection and infusion) was markedly increased in SHR and SHRSP rats with no change in reactivity to sodium nitroprusside. 5. Conversion of AI to AII assessed by the equipressor doses of the hormones which produced a 20-mmHg rise in blood pressure was markedly elevated in SHR (86 +/- 4%) and SHRSP (80 +/- 7%) rats when compared to WKY rats (38 +/- 4%). 6. The marked increase in conversion of AI to AII in hypertensive animals, accompanied by an increased pulmonary degradation of BK in SHR rats, suggests that ACE activity is increased in conscious SHR and SHRSP rats and may participate in the genesis of hypertension in this model of genetic hypertension.
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PMID:Angiotensin converting activity assessed in vivo is increased in hereditary hypertensive rats. 134 16

There is considerable evidence that on the anterior surface of the heart (which is usually supplied by the left anterior descending and the proximal part of the left circumflex coronary arteries), sympathetic efferent reflexes characterized by tachycardia and/or hypertension predominate following experimental or pathological perturbations. These cardiovascular reflexes are accompanied by an increase in presumed nociceptive afferent traffic and, in pathological condition, by pain. In these experiments, there is generally no effect of vagotomy on afferent nerve traffic, and lower cervical and upper thoracic sympathectomies help provide relief from angina. On the other hand, experimental or pathological perturbations involving the inferior-posterior surface of the heart (supplied by the right and distal parts of the left circumflex coronary arteries), are characterized by vagal efferent reflexes, resulting in bradycardia and/or hypotension. These reflexes are accompanied by an increase in vagal afferent nerve traffic and, in pathological conditions, by pain. In these experiments, vagotomy generally abolishes such cardiovascular reflexes, and lower cervical and upper thoracic sympathectomies are not effective in the relief from angina. Although cardiac sympathetic afferents are unquestionably involved in the central transmission of nociceptive information from the heart, it is also likely that there is a contributing role from the vagus in cardiac pain. It is important experimentally to understand the natural stimulus that gives rise to angina. In the clinical situation, a decrease in coronary blood flow or an increase in the metabolic demands of the myocardium due to increased work are obvious precipitating factors which lead to myocardial ischemia. In the experimental situation, occlusion of the coronary arteries is often used as a stimulus which mimics myocardial ischemia. As people who frequently experience angina have varying degrees of coronary artery disease, it is difficult to accept that the state of the coronary arteries of the normal experimental animal bear any resemblance to the state of the coronary arteries under pathological conditions. That is, the gain of homeostatic reflexes, the basal concentrations of neuroactive substances in the plasma, the myocardium and the afferent terminals, the excitability of the afferents, access of chemical mediators (e.g. bradykinin, 5-HT, adenosine, histamine, prostaglandins, potassium, lactate), to afferents, and the overall function of the animal are all significantly different. We have no idea how control mechanisms have been altered in the person with severe coronary artery disease compared to the normal patient or the "normal" experimental animal.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A critical review of the afferent pathways and the potential chemical mediators involved in cardiac pain. 135 Dec 70

1. Chymotrypsin (Cht) administration (14 mg/kg, i.v.) to rats always caused hypertension; hypotension preceded this effect in 64% of the observations (n = 11). 2. A 68% reduction of circulating kininogen but not of angiotensinogen was observed after Cht administration. 3. Cht effects were not affected by captopril, [Sar1-Leu8]-angiotensin II and alpha-adrenoceptor antagonists. In 70% of the observations (n = 10) hypotension was abolished by a mixture of histamine H1- and H2-antagonists. Therefore histamine release may explain hypotension. 4. Cht released in vitro from rat plasma, a substance producing hypertension in the rat and contraction of the guinea-pig ileum. Both effects were antagonized by [Sar1-Leu8]-angiotensin II. 5. In spite of this angiotensin release in vitro, the hypertensive component of the in vivo response to Cht seems to be due to some other substance.
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PMID:Effect of chymotrypsin on rat blood pressure. 135 73

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