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

The main target organ in untreated arterial hypertension (HTA) is the blood vessel wall (BVW) of the high pressure system (conductance and resistance arteries), which is primarily responsible for vital organ integrity. Three major structural changes develop in the BVW in experimental and human HTA: hypertrophy of the smooth muscle (increased thickness of the media), reduction in the amount of elastin and increased interstitial collagen deposition. The latter two structural changes are responsible for the increased stiffness (reduced compliance) that characterizes the BVW in untreated HTA. Angiotensin II, endothelins, nitric oxide, local growth factors (fibroblast-derived growth factor, platelet-derived growth factor, transforming growth factor-beta) and metalloproteinases are involved in BVW remodelling, and represent potential targets for drug action. Angiotensin-converting enzyme (ACE) inhibitors are particularly suited for such actions via their angiotensin II-, bradykinin- and/or interstitial metalloproteinases-dependent actions. Unfortunately, limited data are available on BVW protection with conventional ACE inhibitors. The new ACE inhibitor perindopril differs from most others in terms of BVW protection. In carefully designed morphometric experiments, perindopril has been shown to reduce vascular smooth muscle hypertrophy and to normalize the elastin:collagen ratio in the BVW of hypertensive rats. It has been shown that perindopril is unique in that respect since isradipine, metoprolol, hydralazine and captopril all failed to normalize the media:lumen ratio in the hypertensive rat. The functional counterpart of these in vitro structural findings obtained with perindopril has been demonstrated in human HTA patients; increased brachial artery diameter and compliance were observed after three weeks of perindopril.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The blood vessel as a target organ in hypertension: protective effect of perindopril. 795 36

1. Stroke-prone spontaneously hypertensive rats (SHRSP) were fed a diet with fish meal as the protein source (fish diet) during the progressive stage of hypertension, and its effects on the activity of angiotensin I-converting enzyme (ACE) in serum and vascular tissues and on the aortic elastin content were studied. The effects of the antihypertensive drugs captopril and hydralazine were also studied. 2. Stroke-prone spontaneously hypertensive rats fed the fish diet showed a distinctly lower level (P < 0.05) of serum ACE activity than the control group fed a commercial stock chow. 3. ACE activity was enhanced in the SHRSP which was administered with captopril. 4. Serum ACE activity was similar in the SHRSP receiving the hydralazine treatment and the control group. 5. The thoracic aorta ACE activity was lowered more (P < 0.05) in the fish diet group and the captopril-treated group than in the control group. In the hydralazine-treated group however, the activity was similar to the control group. 6. The ratio of aorta weight to bodyweight was significantly lower (P < 0.05) in the fish diet group and the captopril-treated group than in the control group, but there was no difference in the hydralazine group. Higher levels of aortic elastin were observed in the drug-treated groups (P < 0.05). 7. No differences were seen between the fish diet and captopril-treated groups by electron-microscopy. 8. The results suggest that suppression of hypertrophy and ameliorations of reduction in elasticity of the vascular wall in the SHRSP fed a fish diet were due to inhibition of vascular tissue ACE activity.
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PMID:The vascular tissue angiotensin I-converting enzyme activity and aortic elastin content in stroke-prone spontaneously hypertensive rats fed fish diet. 798 75

In previous studies, we related increased elastolytic activity in pulmonary arteries (PA) with endothelial injury to the later development of PA hypertension in rats. As the mechanism causing the increased PA elastase was unknown, we hypothesized that serum factors which are accessible to vascular smooth muscle cells (SMC) following endothelial injury stimulate their elastolytic activity. To test this, we developed an in vitro assay in which we added [3H]-elastin to cultured vascular SMC after 24 h serum starvation and monitored elastolysis following a further 24 h incubation with fetal bovine serum (FBS). We observed that serum induced increased elastolytic activity in both PA and aorta-derived SMC but not in endothelial cells or SMC with low basal levels of elastolytic activity. Maximum stimulation of SMC elastolytic activity occurred with a concentration as low as 1% FBS and despite elastase inhibitors in serum, suggesting that the activity is confined to the immediate pericellular region where enzyme concentration is high. Serum-stimulated elastolytic activity was not reproduced by growth factors or cytokines known to be associated with vascular disease or to induce release of elastases in other cells. The serum inducing elastolytic activity was heat and acid labile. It was associated with increased elastin adhesion to the 67 kD elastin binding protein on SMC surfaces and was prevented by tyrosine kinase inhibitors but not protein kinase C or A inhibitors. Our studies therefore suggest a mechanism whereby serum induction of SMC elastase requires signalling through the elastin binding protein and activation of tyrosine kinase.
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PMID:Serum-induced vascular smooth muscle cell elastolytic activity through tyrosine kinase intracellular signalling. 802 Dec 92

Effects of two major potent vasoconstrictors, angiotensin II and platelet-derived growth factor, on elastin expression in cultured chick embryonic arterial smooth muscle cells were studied. Platelet-derived growth factor exhibited no effect on elastin synthesis nor its mRNA level but stimulated (1.5-fold) cell proliferation slightly. Angiotensin II inhibited elastin synthesis dose- and time-dependent manner with a maximum suppression of sixty percent of control at a concentration of 10 microM for 18 h treatment. The suppression was accompanied with a comparable decrease in elastin mRNA level. The inhibition was blocked by addition of Sar1,Ala8-angiotensin II and 8-bromo-cGMP. It showed no effect on cell proliferation. Angiotensin II appears to inhibit elastin synthesis through the interaction with its receptor and the modulation of intracellular Ca2+ level. Thus angiotensin II, not platelet-derived growth factor, can exert a profound effect on the extracellular matrix composition in arterial walls, leading to an arterial change in hypertension or atherosclerosis.
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PMID:Elastin synthesis is inhibited by angiotensin II but not by platelet-derived growth factor in arterial smooth muscle cells. 804 11

The consequences of hypertension and aging on cardiovascular structure and function are reputed to be similar, suggesting that blood pressure plays a role in the aging process. However, the exact relationship between aging, blood pressure, and the arterial structure-function relationship has not been demonstrated. To test the effects of aging, renin-angiotensin system, and pressure on the arterial wall, 20 normotensive male WAG/Rij rats were killed at 6, 12, 24, and 30 mo of age and compared with similar groups treated with an angiotensin (ANG)-converting enzyme inhibitor (ACEI), perindopril. Arterial function was determined by a systemic hemodynamic study and by in situ measurement of carotid compliance. Arterial wall structure was determined by histomorphometric and biochemical methods. Aging did not significantly modify blood pressure, but ACE inhibition decreased blood pressure significantly from 6 to 30 mo. Plasma renin activity decreased with age and increased with ACEI. Plasma atrial natriuretic factor increased with age and was significantly decreased with ACEI. Absolute and relative left ventricular weight increased with age, and ACEI delayed these increases. Arterial wall stiffness increased with age, as shown by a significant decrease in systemic and local arterial compliance and by an increase in aortic characteristic impedance. The increase in carotid wall compliance after poisoning of smooth muscle contractile function (KCN) was greater in young (6- and 12-mo old) than in old (24- and 30-mo old) rats. Chronic ACEI treatment increased basal carotid compliance values slightly and did not change KCN carotid compliance. The aortic and carotid luminal size increased regularly with age. Aging was associated without any change in absolute elastin content. In contrast, collagen content increased with aging. Aging was also associated with an increase in medial thickness. Medial thickening was mainly due to smooth muscle hypertrophy. Aging was associated with intimal proliferation, which became progressively thicker and collagen rich. ACEI treatment did not prevent aortic lumen enlargement but significantly postponed the increase in medial and intimal thickening. Biochemical determinations of the aortic wall components confirmed the morphometric data. In conclusion, the age-dependent large artery enlargement and stiffening were observed both in normotensive rats and in those rats whose blood pressure was lowered by ACEI. This suggests that aging and blood pressure affect arterial wall structure and function by different mechanisms.
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PMID:Effect of chronic ANG I-converting enzyme inhibition on aging processes. II. Large arteries. 804 14

In hypertension, the thickening of the arterial wall by an increase in the cellular mass and collagen and elastin content may be considered to be an adaptive response to the high blood pressure. Positive and negative feedback systems play a role in the hypertension-vascular hypertrophy couple. Increased wall stress associated with stretching of the smooth muscle acts as a mechanical agonist of cellular growth in synergy with plasma or autocrine growth factors. In general, vascular hypertrophy ceases when the stress returns to normal. However, the increase in cell mass may result in an increase in systemic vascular resistance due to muscular hypertonicity and lead to an amplification of the hypertensive condition. The mechanisms of mechano-transduction are not fully understood. Moreover, genetic vascular changes affecting the structure of the vessels, the sensitivity to vasoactive substances or the geometry of the vascular system can also induce hypertension.
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PMID:[Mechanisms of vascular hypertrophy in hypertension]. 821 82

The histopathology, ultrastructure, and clinicopathologic correlations in six patients with cardiac failure and iron encrustation of lung elastic tissue were examined at autopsy. Transmission electron microscopy (TEM) and energy dispersive x-ray analysis were applied to two cases. Of the group, five patients had cardiac failure due to systemic hypertension (4 patients), valvular disease (4 patients), or coronary atherosclerosis (4 patients). Biventricular failure in one patient was associated with sleep apnea. Both iron and calcium, identified by histochemical stains, impregnated degenerated alveolar and vascular elastic fibers and were associated with a foreign body reaction and focal interstitial fibrosis. Energy dispersive x-ray analysis and TEM demonstrated iron and calcium on the microfibrillar portion of elastin. Morphometry indicated vascular changes of pulmonary venous hypertension. The authors concluded that mineral deposition probably represents nonspecific precipitation of metallic ions on altered elastic fibers in patients with cardiac failure. "Mineralizing elastosis" potentially contributes to lung restriction and, occasionally, can be a source of diagnostic confusion.
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PMID:Mineralizing pulmonary elastosis in chronic cardiac failure. "Endogenous pneumoconiosis" revisited. 827 51

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

It has recently been proposed that in rat models of genetic hypertension, supplemental dietary potassium preserves release of endothelium-derived relaxing factor independently of its capacity to either attenuate hypertension or increase plasma potassium. To test this hypothesis in Dahl salt-sensitive rats given sodium chloride (4%) for 3 weeks, we supplemented dietary potassium (2.1%) with either KCl (n = 16) or KHCO3 (n = 16). Compared with unsupplemented rats (n = 16), rats supplemented with either potassium salt had a lower mean arterial pressure and a greater release of endothelium-derived relaxing factor, as assessed from acetylcholine-induced relaxation of precontracted aortic rings. However, the maximum relaxation response to acetylcholine correlated inversely with blood pressure (r = -.82, P < .001), not only in the KCl (r = -.68, P < .002) and KHCO3 (r = -.77, P < .001) groups but also in unsupplemented rats (r = -.86, P < .001). With potassium supplementation, plasma potassium concentrations measured between 4 and 6 PM did not increase, but those measured between 4 and 6 AM did increase (P < .05). In isolated ring segments, aortic compliance was greater in both the KCl and KHCO3 groups than in unsupplemented rats (0.015 and 0.017 vs 0.009 mm2/mm Hg) (P < .01). This greater compliance could not be related to differences in blood pressure, plasma potassium, or collagen or elastin content of the aortic wall.(ABSTRACT TRUNCATED AT 250 WORDS)
Hypertension 1993 Sep
PMID:Potassium preserves endothelial function and enhances aortic compliance in Dahl rats. 834 24

A nonhypotensive dose of atrial natriuretic peptide (ANP) was infused (60 pg/kg body wt per day s.c. by osmotic pump) for 25 days in 16-week-old normotensive Wistar-Kyoto rats (WKYs, n = 12) and age-matched spontaneously hypertensive rats (SHRs, n = 12). During the infusion period, systolic blood pressure, urinary volume, and cyclic guanosine monophosphate (cGMP) excretion/12 hr were measured once a week in both groups. Then mechanical and morphological properties of the arterial wall and plasma ANP levels were assessed and compared with those from control groups of SHRs (n = 8) and WKYs (n = 8) receiving a saline vehicle. The compliance (CC) of the in situ localized carotid artery was measured for pressures ranging from 25 to 175 mm Hg under control conditions and after "poisoning" of smooth muscle tone by potassium cyanide. After pressure fixation, the medial thickness, elastin and collagen contents, and the size and number of nuclei were measured in the thoracic descending aorta. In WKYs, ANP did not modify either mechanical or structural properties of the arterial wall or biochemical parameters. Conversely, in ANP-treated SHRs, CC was significantly increased compared with untreated SHRs under basal conditions (p < 0.03) and after potassium cyanide poisoning (p < 0.02). Structural properties were also modified by ANP in SHRs, i.e., medial thickness (129.3 +/- 4.1 versus 113.1 +/- 3.3 microns, p < 0.01) and nuclear size (8.81 +/- 0.28 versus 5.52 +/- 0.20 microns 2, p < 0.0001) in untreated and treated SHRs, respectively. Furthermore, urinary volume and cGMP content were significantly increased during ANP infusion in treated SHRs (p < 0.05). The present results indicate concomitant modifications of mechanical and structural properties of the arterial wall in SHRs chronically treated with low doses of ANP. These long-term effects of ANP could be involved in the remodeling of the arterial wall observed during hypertension and could have beneficial effects on cardiovascular diseases in chronic sustained hypertension.
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PMID:Effect of a nonhypotensive long-term infusion of ANP on the mechanical and structural properties of the arterial wall in Wistar-Kyoto and spontaneously hypertensive rats. 838 30


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