Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Evidence from experiments in conscious, instrumented dogs shows that hypertension from renal artery stenosis is due to: (i) the stimulus, the mechanical resistance of the stenosis; and (ii) the secondary responses to this, especially angiotensin II (initially) and cardiovascular hypertrophy. 2. The hydraulic resistance of the stenosis is responsible for about 20-25% of the rise in blood pressure. 3. Angiotensin II is initially the most important secondary response to the stenosis. Within days, however, other as yet undetermined factors become dominant in the maintenance of the hypertension. The most important of these factors is probably cardiovascular hypertrophy. 4. These secondary factors are homeostatic, in that they mitigate the effects of stenosis on renal function.
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PMID:Renovascular hypertension: information from experiments using conscious dogs. 203 86

In chronic models of hypertension such as the spontaneously hypertensive rat (SHR), thickening of the media of large arteries occurs mainly through smooth muscle cell (SMC) hypertrophy accompanied by DNA replication resulting in large polyploid cells. In resistance vessels of SHR, medial hypertrophy occurs through a hyperplastic response. It has been suggested that this hyperplasia is due to mitogens such as platelet-derived growth factor (PDGF), while the hypertrophied polyploid cells occur from stimulation by angiotensin II from within the vessel wall. Angiotensin II activates many of the same cellular pathways as PDGF, including stimulation of phospholipase C, mobilization of intracellular calcium and activation of Na+/H+ exchange. Both induce transient increases in the proto-oncogenes c-fos and c-myc. However, a possible explanation for the difference in SMC response may be involvement of an intracellular pathway stimulated by PDGF (but not by angiotensin II), such as stimulation of JE (a cytokine-like molecule), which may activate transcriptional events necessary for mitogenesis. In atherosclerosis vascular hypertrophy occurs in the form of focal intimal thickening and results from hyperplasia of diploid SMC and their greatly increased production of extracellular matrix, (particularly collagen) and the accumulation of intra- and extracellular lipid. The SMC involved in atherogenesis are phenotypically modified compared with the SMC of undiseased regions, and amongst other features have a lower volume fraction of myofilaments (Vvmyo). Associated with modulation to a low Vvmyo are increases in SMC expression of mRNA for collagens type I (alpha 1 and alpha 2) and type III (alpha 1), elastin, fibronectin, as well as massive increases in collagen protein (26- to 45-fold), glycosaminoglycans (5-fold), and lipid accumulation (7-fold).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Molecular biology of vascular hypertrophy. 203 94

Angiotensin II is an important effector molecule controlling blood pressure and volume in the cardiovascular system. Its importance is manifested by the efficacy of angiotensin-converting enzyme inhibitors in the treatment of hypertension and congestive heart failure. Angiotensin II interacts with two pharmacologically distinct subtypes of cell-surface receptors, AT1 and AT2. AT1 receptors seem to mediate the major cardiovascular effects of angiotensin II. Here we report the isolation by expression cloning of a complementary DNA encoding a unique protein with the pharmacological specificity of a vascular AT1 receptor. Hydropathic modelling of the deduced protein suggests that it shares the seven-transmembrane-region motif with the G protein-coupled receptor superfamily. Knowledge of the AT1 receptor primary sequence should now permit structural analysis, definition of the angiotensin II receptor gene family and delineation of the contribution of AT receptors to the genetic component of hypertension.
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PMID:Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. 204 70

The clinical efficacy and indications for Angiotensin II (AT II)-induced hypertension chemotherapy were evaluated as a drug delivery system in 101 patients with advanced carcinoma. The sites of primary tumor studied included stomach (44), pancreas (18), colon (16), esophagus (6), bile duct (4), liver (3), breast (7) and 3 other single organs. Seventy four cases had distant metastases (lymph node (25), liver (29), peritoneum (16), and lung (4)). Additionally, the protocol was used 12 cases as postoperative adjuvant chemotherapy and 15 cases following exploratory laparotomy. The blood pressure was elevated to a level 1.5 times base-line. The regimens used consisted of MMC + ADR (55), FAM (38) and CDDP (8). The dosages administered were MMC 7 mg/m2, ADR 14 mg/m2 and 5-FU 350 mg/m2. The cancer chemotherapy protocol with AT II was repeated for an average of 2.6 cycles with a 2-3 week interval. The drug concentration in tumor tissues was increased 1.7 fold by AT II treatment. The response rate was 15.8% (CR 7 and PR 9), and in those patients with lymph node, liver and peritoneal metastases was 48.0, 6.9 and 6.3%, respectively. The serum levels of tumor markers decreased in 9 patients. Subjective symptoms, such as hoarseness, edema and pain, were improved. The mean survival in patients with distant metastasis who responded was 343 days, and in nonresponders was only 168 days (p less than 0.05). The side effects of this therapy were slight, typically being grade 1 and 2. Thus, the chemotherapeutic agents studied in conjunction with AT II were effective in patients with lymph node metastasis. Additionally, this regimen could be performed safely with minimal side effects.
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PMID:Clinical evaluation of chemotherapy under angiotensin II-induced hypertension in patients with advanced cancer. 213 Jul 94

Cardiac hypertrophy is characterized by marked abnormalities in the contraction/relaxation pattern of the heart. For example, delayed relaxation is a prominent feature, impairing ventricular filling and coronary flow. In intact heart preparations the relative contribution of fibrosis and of the myocardial cell itself to these abnormalities cannot be correctly assessed. Biochemical studies on the mechanisms of impaired contraction and relaxation and hypertensive heart failure are hampered by the fact that 75% of all heart cells are non-myocytes. We therefore established the model of the isolated calcium-tolerant, adult rat cardiomyocyte as a new approach to the investigation of these problems. Contractility was measured using a videomicroscope system with high time resolution (1 ms). Angiotensin II induced a marked relaxation delay in the cardiomyocyte from normotensive rats and showed a moderate positive inotropic effect, whereas isoproterenol had a strong positive inotropic effect but accelerated relaxation. Therefore, angiotensin II is capable of inducing a relaxation delay even in the absence of coronary ischaemia or hypertension. These first results show that the isolated cardiomyocyte model may be a useful approach to investigating the mechanisms of hypertensive heart disease.
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PMID:Isolated myocardial cells: a new tool for the investigation of hypertensive heart disease. 214 54

1. Angiotensin II (ANG II) and atrial natriuretic peptide (ANP) are functionally antagonistic circulating hormones involved in blood pressure and body fluid regulation. An inappropriate atrial secretion of ANP has been implicated in the pathogenesis of hypertension, but clinical and experimental results on the role of ANP in hypertension are still conflicting. 2. In the brain both peptides have been localized in close proximity, preferentially in areas involved in central cardiovascular, electrolyte and volume control. ANP was shown to inhibit ANG II-induced drinking, release of pituitary hormones and natriuresis, and to induce sodium retention when given alone. 3. These findings suggest that also in the brain ANG II and ANP exert functionally antagonistic effects. However, in contrast to their peripheral effects, ANG II induces natriuresis while ANP appears to cause antinatriuresis in the brain.
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PMID:Atrial natriuretic peptide (ANP) as a neuropeptide: interaction with angiotensin II on volume control and renal sodium handling. 214 93

Although alterations in Ca2+ metabolism have been demonstrated in subcultured aortic myocytes of spontaneously hypertensive rats (SHR), changes in intact tissue have not been described. This study compares Ca2+ metabolism in intact mesenteric resistance arteries and in myocytes that were derived from mesenteric arteries and maintained in primary and long-term culture. Using fura-2, basal levels of Ca2+ were found to be similar in intact vessels of SHR and Wistar-Kyoto normotensive rats (WKY), and in primary and first-passage myocytes of the two strains. During subculture, basal levels of Ca2+ became elevated in myocytes of SHR. When norepinephrine-induced Ca2+ mobilization was examined, the threshold of resistance arteries was lower in SHR, but differences were not detected with higher concentrations of the agonist. Norepinephrine-induced Ca2+ mobilization also did not differ between primary myocytes of the two strains. Angiotensin II elicited greater intracellular Ca2+ responses in myocytes of SHR at passages 1, 3 and 5. Cell growth was assessed at each passage level. While no strain differences were detected in primary, first- and second-passage cells, the growth rate became elevated in SHR in subsequent passages. These results are consistent with the hypothesis that vascular myocytes cultured from SHR with established hypertension exhibit differences in Ca2+ metabolism that are not present in the intact vessel wall. Furthermore, intracellular Ca2+ appears to be elevated in myocytes of SHR when the rate of proliferation is increased.
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PMID:Intracellular Ca2+ metabolism of isolated resistance arteries and cultured vascular myocytes of spontaneously hypertensive and Wistar-Kyoto normotensive rats. 215 55

The reaction of the renin-angiotensin system to acute angiotensin converting enzyme inhibition was investigated in a single-blind, crossover study in nine normal volunteers receiving two out of three regimens in random order: the new converting enzyme inhibitor benazepril (20 mg once or 5 mg four times at 6-hour intervals) or enalapril (20 mg). Plasma converting enzyme activity, drug levels, angiotensin I and angiotensin II, active renin, and aldosterone were measured before and 1-4 hours and 14-30 hours after drug intake. Baseline in vitro plasma converting enzyme activity was 97 +/- 15 nmol/ml/min (mean +/- SD) when Hip-Gly-Gly was used as substrate, but with carbobenzoxy-Phe-His-Leu (Z-Phe-His-Leu) or angiotensin I as substrate it was only 20 +/- 4 and 1.7 +/- 0.3 nmol/ml/min, respectively. Discriminating power at peak converting enzyme inhibition was enhanced with the two latter substrates. In vivo converting enzyme activity was estimated by the plasma angiotensin II/angiotensin I ratio, which correlated well with in vitro converting enzyme activity using Z-Phe-His-Leu as substrate (r = 0.76, n = 252). Angiotensin II levels returned to baseline less than 24 hours after drug administration, whereas in vitro and in vivo converting enzyme activity remained considerably inhibited and active renin together with angiotensin I levels were still elevated. A close linear relation was found between plasma angiotensin II and the angiotensin I/drug level ratio (r = 0.91 for benazeprilat and r = 0.88 for enalaprilat, p less than 0.001). Thus, plasma angiotensin II truly reflects the resetting of the renin-angiotensin system at any degree of converting enzyme inhibition. The ratio of plasma angiotensin II to angiotensin I represents converting enzyme inhibition more accurately than in vitro assays, which vary considerably depending on substrates and assay conditions used.
Hypertension 1990 Nov
PMID:Determinants of angiotensin II generation during converting enzyme inhibition. 217 61

Angiotensin II has recently been shown to exert potent control over sodium and water absorption in the proximal convoluted tubule. This transport stimulation is effected by receptors on both the luminal and basolateral membranes of cells located predominantly in the early, S1 proximal tubule. Angiotensin II increases transport primarily by a Gi protein-mediated reduction in intracellular cyclic adenosine monophosphate, which enhances the affinity of the Na(+)-H+ antiporter. Change in early proximal acidification ultimately causes alteration in the amount of sodium chloride leaving the proximal tubule and entering the urine. These direct tubular transport actions by angiotensin II may participate importantly in various physiological actions of the kidney, including the renal response to change in dietary sodium intake and in extracellular volume, as well as in pathophysiological processes such as hypertension.
Hypertension 1990 May
PMID:Angiotensin II: a powerful controller of sodium transport in the early proximal tubule. 218 49

Interactions between extracellular fibronectin and vascular cells are thought to influence the phenotype of those cells. To determine if changes in fibronectin expression accompany the phenotypic changes of vascular tissue characteristic of experimental hypertension, steady state mRNA levels for fibronectin were determined in aortae of normotensive and hypertensive rats. A 3-6-fold increase in fibronectin mRNA was observed in aortic tissue of hypertensive rats following 3 weeks of treatment with deoxycorticosterone and salt, whereas if rats were treated only with deoxycorticosterone or salt alone, no changes occurred. The changes were reversed by normalization of blood pressure. The increases observed were localized to aorta and not to the periaortic tissue. Angiotensin II infusion using osmotic minipumps also caused an increase in fibronectin expression. Age-dependent increases in aortic fibronectin mRNA occurred in several rat strains, and the combined effects of hypertension and aging were greater than either variable alone. A clear distinction between the expression of fibronectin mRNA and that for collagen or tropoelastin were found in hypertensive and aging models. Aortic fibronectin was also increased in the hypertensive rats as determined by Western blot analysis. The findings indicate that elevation in blood pressure increases fibronectin expression in rat aorta and suggest that such changes may influence the aortic cellular responses to hypertension.
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PMID:Effect of hypertension on fibronectin expression in the rat aorta. 225 39


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