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

After microsurgical dissection of the thoracic aorta of normotensive rats, biochemical and morphological comparisons were performed between the intima-media and adventitia. The DNA content, wet weight, and dry defatted weight of the adventitia were half that of the intima-media. Collagen was the main component of the adventitia (collagen greater than nonfibrous protein greater than elastin) whereas elastin was the main protein in the intima-media (elastin greater than nonfibrous protein greater than collagen), and the results correlated with morphological observations. Hypertension induced by aortic ligation between the renal arteries resulted in rapid elevations in circulating humoral factors and blood pressure. A sixfold increase in DNA synthesis was observed in the adventitia (p less than 0.001), resulting in a significant increase in DNA content as early as 6 days after aortic ligation (75% increase; p less than 0.001). Increased DNA replication was accompanied by elevations in nonfibrous protein and elastin contents. Autoradiograms showed labeled adventitial fibroblasts throughout the thickness of the adventitia and along the entire length of the aorta and smaller vessels. DNA synthesis and content and labeled smooth muscle cells were increased in the intima-media. These studies indicate that the adventitia participates in the development of vascular hypertrophy and arterial disease produced by aortic ligation.
Hypertension 1988 Feb
PMID:Increased DNA replication in the arterial adventitia after aortic ligation. 334 48

Pregnancy-induced hypertension was induced in five ewes (gestational day 135; term 150 days) by 72 hours of food deprivation. Maternal arterial pressure, uterine blood flow, platelet function, renal function, and plasma levels of 6-ketoprostaglandin F1 alpha and thromboxane B2 were measured before and during hypertension and after three intravenous injections of U-63,557A; sodium 5-(3'-pyridinylmethyl) benzofuran-2-carboxylate, monohydrate (30 mg/kg every 8 hours). Blood pressure increased (p less than 0.03), and returned to normal after U-63,557A. Left uterine artery blood flow increased after U-63,557A (p less than 0.03). Creatinine clearance decreased during hypertension (p less than 0.03) and increased after U-63,557A. Urine protein increased during hypertension (p less than 0.03) and decreased after treatment. Platelet count dropped during hypertension (p less than 0.03) and was elevated after treatment. Collagen lag phase decreased during hypertension (p less than 0.03) and increased after treatment. After U-63,557A, 6-ketoprostaglandin F1 alpha levels were higher (p less than 0.04) than baseline or hypertensive values. Administration of a thromboxane synthetase inhibitor caused resolution of hemodynamic, renal, and coagulation dysfunctions that occurred in ovine pregnancy-induced hypertension.
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PMID:Beneficial effects of U-63,557A, a thromboxane synthetase inhibitor, in an ovine model of pregnancy-induced hypertension. 360 54

Collagen synthesis is increased in the aortas, mesenteric arteries, and to a lesser extent, in the hearts of rats either made hypertensive with desoxycorticosterone acetate-salt or that are spontaneously hypertensive. Several markers of collagen biosynthesis were shown to be increased, including prolyl hydroxylase (EC 1.14.11.2; proline, 2-oxoglutarate dioxygenase), prolyl hydroxylase-related antigen, total collagen content, and the incorporation of [(3)H]proline into total protein and into collagen. The antihypertensive agents chlorothiazide and reserpine, when administered before the onset of hypertension in the rats treated with desoxycorticosterone acetate-salt, prevented or diminished the increase in collagen biosynthesis. When reserpine was given after the onset of hypertension, prolyl hydroxylase activity was decreased concomitant with the decrease in blood pressure. Treatment with reserpine is particularly effective in diminishing arterial prolyl hydroxylase activity.
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PMID:Increased collagen synthesis in blood vessels of hypertensive rats and its reversal by antihypertensive agents. 437 97

Collagen synthesis and content have been shown to be elevated in the arterial wall and heart of hypertensive animals. These increases in collagen synthesis and content have been implicated in the maintenance of raised blood pressure. Inhibitors of collagen synthesis, beta APN and 3,4-dihydroproline, were shown to delay the onset of hypertension and reverse established hypertension. Therapeutic intervention with antihypertensive drugs resulted in a decrease in arterial collagen synthesis and a reversal of cardiac hypertrophy. In some instances (i.e., DOCA-salt), chronic administration of antihypertensive drugs caused a restructuring of the arterial wall and resulted in an apparent remission of the hypertensive disease.
Hypertension
PMID:Synthesis of collagen in cardiac and vascular walls. 624 Apr 53

Specimens from the uterine wall were obtained from 16 patients at 31 to 40 weeks of pregnancy: 10 underwent surgical procedures for a hypertensive disorder and six for abnormality of the birth canal or faulty presentation. Collagen types I, III, and V and fibronectin antibodies were used for immunohistologic studies. Collagen types I and V were located mainly around single cells, but type III and fibronectin were found mainly around cell bundles. Collagenous structures in the uterine muscle of patients with hypertensive disorder in pregnancy were torn. Abundant fibronectin fluorescence was detected in the lobuli within the disrupted tissue. Disruption of the uterine structure correlated with the amount of urinary protein excreted.
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PMID:Collagen types and fibronectin in the uterine muscle of normal and hypertensive pregnant patients. 638 Feb 93

Collagen synthesis, content, and concentration were determined in the hypertrophied intima media of thoracic aortas from 10-, 15-, and 20-week-old spontaneously hypertensive rats (SHR). Although the rates of aortic collagen synthesis declined with age, the dry weight of the intima media and the total collagen content increased proportionally. Collagen concentration thus remained unchanged. Methyldopa was administered orally to SHR when they were 12 to 15 weeks of age, when their body weight were identical to the untreated group. Blood pressure and the degree of aortic medial hypertrophy, judged by medial dry weight per kilogram body weight, were significantly lower compared with untreated SHR. Collagen synthesis was likewise decreased to a mean rate not significantly higher than age-matched normotensive Wistar-Kyoto controls. This reduction in collagen synthesis, however, was not sufficient to decrease measurably the total collagen content of the aortas compared with untreated SHR. Since medial dry weights were lower in the treated rats, collagen concentration in aortas from SHR given methyldopa for 3 weeks was actually increased. The increase in collagen concentration also suggests that medial hypertrophy was reversed.
Hypertension
PMID:Collagen metabolism and reversal of aortic medial hypertrophy in spontaneously hypertensive rats treated with methyldopa. 730 9

In arterial hypertension or congestive heart failure, myocardial fibrosis is associated with an activated renin-angiotensin-aldosterone system (RAAS). This reactive fibrosis presents as an excessive accumulation of fibrillar collagen within the normal connective tissue structures of the myocardium in either ventricle, irrespective of its haemodynamic load. It therefore would appear that circulating (hormonal) and not haemodynamic factors are responsible for this adverse fibrous tissue response. The cardiac fibroblast expresses mRNA for types I and III collagens, the major fibrillar collagens in the heart, and for collagenase or matrix metalloproteinase 1 (MMP 1), the key enzyme for interstitial collagen degradation. Therefore, adult rat cardiac fibroblasts were cultured to ascertain whether the RAAS effector hormones angiotensin II (Ang II) or aldosterone (Aldo) directly stimulate collagen synthesis or inhibit MMP 1 production. Collagen synthesis, determined by 3H-proline incorporation and MMP 1 activity determined by degradation of 14C-collagen, were measured under serum-free conditions in confluent, quiescent fibroblasts after 24 h incubation with Ang II or Aldo over a wide range of concentrations (10(-11) -10(-6) M). In addition, collagen synthesis was measured after incubation with the mineralocorticoid, dexoycorticosterone (DOC), or the prostaglandin, PGE2. Collagen synthesis, normalized per total protein synthesis, increased significantly in a dose-dependent manner after incubation with either mineralocorticoid hormone, Aldo or DOC, or after incubation with Ang II compared with untreated control cells. In contrast, collagen synthesis was significantly decreased with PGE2 treatment. This increase in collagen synthesis in Ang II or mineralocorticoid-stimulated fibroblasts could be completely abolished by Ang II type 1 or mineralocorticoid receptor antagonists, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hormonal regulation of cardiac fibroblast function. 755 72

Myocardial fibrosis has been investigated in 3-, 16-, and 24-mo-old normal rats and also in 24-mo-old rats subjected to deoxycorticosterone acetate (DOCA)-salt treatment-induced-hypertension. Collagen content was assessed both histologically and by hydroxyproline assay. Type I and III procollagen mRNA levels were quantitated by Slot Blot analyses. Aging is associated with fibrosis as shown both biochemically (hydroxyproline concentration in 3-, 16-, and 24-mo-old rats was 0.70 +/- 0.05, 0.92 +/- 0.07, and 1.57 +/- 0.13 mg/g of left ventricle, respectively, P < 0.05 and P < 0.0001 vs. 3 mo) and histologically. By contrast, type I procollagen mRNA levels decreased during aging (from -63%, P < 0.001 in 16-mo-old rats and -51%, P < 0.01 in 24-mo-old rats vs. 3-mo-old rats) as well as type III procollagen mRNA levels. DOCA-salt treatment in 24-mo-old rats had no effect on either the degree of fibrosis or the mRNA levels. We conclude that nonsynchronous changes in myocardial collagen mRNA and protein occur during aging, indicating translational and/or posttranslational mechanisms in collagen regulation. Hypertension during senescence did not modify collagen deposition at either the protein or mRNA levels.
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PMID:Nonsynchronous changes in myocardial collagen mRNA and protein during aging: effect of DOCA-salt hypertension. 781 Jul 23

Myocardial fibrosis is associated with an activated renin-angiotensin-aldosterone system (RAAS). In renovascular hypertension, this presents as a reactive perivascular and interstitial fibrosis in not only the pressure overloaded, hypertrophied left ventricle but also the normotensive, nonhypertrophied right ventricle. It therefore would appear that circulating hormonal and not hemodynamic factors are responsible for this adverse fibrous tissue response. To ascertain whether the RAAS effector hormones angiotensin II (AII) or aldosterone (ALDO) directly stimulate collagen synthesis or inhibit collagenase production we used cell culture. Adult rat cardiac fibroblasts (Fb) were cultured since these cells express mRNA for types I and III collagens, the major fibrillar collagens in the heart, and collagenase or matrix metalloproteinase 1 (MMP 1), the key enzyme for interstitial collagen degradation. Collagen synthesis, determined by 3H-proline incorporation, and collagenase activity were measured in confluent, quiescent Fb after 24 h incubation with various concentrations of AII or ALDO (10(-11)-10(-6)M) in the presence or absence of either 10(-5)M type 1 (DuP 753) and type 2 (PD 123177) AII or 10(-9)-3 x 10(-6)M ALDO (spironolactone) receptor antagonists, respectively. Collagen synthesis, normalized per total protein synthesis, increased significantly (P < 0.005) after incubation with either 10(-9)M ALDO (5.9 +/- 1.0%) or 10(-7)M AII (5.3 +/- 1.2%) compared with untreated control cells (2.9 +/- 0.5%) of the same passage (p6-p10). This increase in collagen synthesis could be completely abolished by either types 1 or 2 AII receptor antagonists in AII stimulated Fb or the competitive ALDO receptor antagonist, spironolactone, at equimolar concentration in ALDO stimulated Fb. AII significantly decreased collagenase activity which could be completely abolished by PD 123177, but not DuP 753, while ALDO had no effect on collagenase activity. The mineralocorticoid, ALDO, stimulates collagen synthesis in cultured adult rat cardiac Fb in concentrations similar to those found in plasma in renovascular hypertension and this response appears to occur via type I corticoid receptors. AII appears to stimulate collagen synthesis by both type 1 and 2 AII receptors, but only in high concentrations that could be generated locally within the myocardium. In addition, AII unlike ALDO inhibits collagenase activity that could be attenuated only by type 2 receptor blockade. These findings suggest a direct interaction between ALDO, AII and cardiac Fb in mediating myocardial fibrosis in hypertensive heart disease.
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PMID:Collagen metabolism in cultured adult rat cardiac fibroblasts: response to angiotensin II and aldosterone. 796 49

The effects of long-term angiotensin-converting enzyme (ACE) inhibitor treatment with perindopril 2 mg/kg/day, by gavage, for 3 months on the mechanical function and structure of large arteries were studied in adult spontaneously hypertensive rats with established hypertension. Hemodynamic parameters, including instantaneous aortic blood flow and pressure, were recorded under anesthesia at the end of the treatment period. Systemic arterial compliance was calculated from aortic pressure and flow recordings; passive mechanical properties of the in situ localized carotid artery were measured. Histologic and morphologic parameters of the aortic media, including cross-sectional area and thickness, size, and density of smooth muscle nuclei and of elastin and collagen fibers, were measured using an automated image analysis system. ACE inhibitor treatment significantly decreased mean arterial pressure (-27%, p < 0.001) and total peripheral resistance (-30%, p < 0.05) while cardiac output was increased (29%, p < 0.05). Systemic arterial compliance and carotid compliance were both increased by treatment (63%, p < 0.05, and 83%, p < 0.05, respectively). Morphometric assessment of vascular structure showed that ACE inhibitor treatment significantly decreased medial cross-sectional area (-36%, p < 0.001) and thickness (-16%, p < 0.001) by affecting smooth muscle cell hypertrophy (nucleus size decreased by 26%, p < 0.05) without changes in smooth cell number. Collagen density was decreased by treatment (-42%, p < 0.05), whereas elastin density was not affected by treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Long-term effects of angiotensin-converting enzyme inhibition on the arterial wall of adult spontaneously hypertensive rats. 832 70


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