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

1. Endothelium-dependent vascular regulation was investigated in mesenteric resistance arteries of Goldblatt two kidney-one clip (2K1C) renovascular hypertensive rats. 2. Third order branches of mesenteric arteries were dissected free and mounted on glass cannulae in an organ chamber. Changes in vascular diameter were measured in pressurized and perfused arteries with a video dimension analyzer. 3. Acetylcholine evoked endothelium-dependent relaxations that were much more pronounced with intraluminal than with extraluminal application. In 2K1C rats the relaxation induced by intraluminal, but not extraluminal acetylcholine was decreased compared to normotensive Wistar Kyoto rats (WKY). Increased duration of hypertension further decreased the response to intraluminal but not extraluminal acetylcholine. 4. Endothelin-1 and noradrenaline caused contractions which were augmented by removal of the endothelium. This augmentation was reduced in 2K1C rats compared to WKY; the difference was small with noradrenaline but more pronounced with endothelin-1. 5. In arteries without endothelium the sensitivity, but not the maximal contraction to endothelin-1 was lower in 2K1C rats, while the response to noradrenaline was not different in 2K1C rats and WKY. The sensitivity to the peptide was not further affected by increasing the duration of hypertension. 6. Thus, renovascular hypertension leads to an impaired intraluminal, but not extraluminal activation of the release of endothelium-derived relaxing factor and a decreased inhibitory effect of the endothelium against endothelin-1- and noradrenaline-induced contractions in mesenteric resistance arteries. Furthermore, the sensitivity, but not the maximal response of vascular smooth muscle to endothelin-1 was reduced.
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PMID:Renovascular hypertension impairs formation of endothelium-derived relaxing factors and sensitivity to endothelin-1 in resistance arteries. 179 2

We measured the concentrations of three principal products of the renin-angiotensin system and seven of their metabolites in the plasma of anesthetized normal dogs and in dogs 24 hours after bilateral nephrectomy. The levels of the angiotensin peptides were measured by high-performance liquid chromatography combined with radioimmunoassay using three specific antibodies that recognized different epitotes in the sequences of angiotensin I, angiotensin II, and angiotensin-(1-7). The analysis revealed that angiotensin-(1-7) is present in the plasma of intact (4.9 +/- 2.2 fmol/ml) and nephrectomized (0.5 +/- 0.5 fmol/ml) dogs. An intravenous injection of purified hog renin (0.01 Goldblatt unit/kg) increased plasma levels of angiotensin I, angiotensin II, and angiotensin-(1-7) both before and after nephrectomy. These changes were associated with parallel increases in the concentrations of fragments of the three parent peptides. Administration of MK-422 led to the disappearance of circulating angiotensin II and its fragments both before and after a second injection of the same dose of renin. In contrast, MK-422 augmented the plasma levels of both angiotensin I and angiotensin-(1-7). The concentrations of these two peptides, but not the blood pressure, were again augmented by a second injection of renin given after blockade of converting enzyme. These effects were observed both before and after bilateral nephrectomy. These findings show that angiotensin-(1-7) circulates in the blood of normal and nephrectomized dogs. In addition, we found that angiotensin-(1-7) is generated in the blood from the cleavage of angiotensin I through a pathway independent of converting enzyme (EC 3.4.15.1).
Hypertension 1991 Feb
PMID:Angiotensin-(1-7). A member of circulating angiotensin peptides. 184 40

1. Using a ribonuclease-protection assay, renin mRNA levels were compared in the kidneys, livers, brains, hearts and adrenal glands of two-kidney, one-clip Goldblatt hypertensive rats with those of age-matched control rats at 4 weeks ('early') and 20 weeks ('chronic') after clipping, and in the kidneys and adrenal glands of rats treated for 3 weeks with deoxycorticosterone and salt (deoxycorticosterone-salt hypertension) with those of control rats. 2. While marked changes were observed in kidney renin mRNA levels in all three experimental groups compared with their respective controls, in most of the extra-renal tissue studied minimal, if any, difference was seen in renin mRNA levels between the hypertensive and control rats. 3. The findings suggest that in these extra-renal tissues renin gene expression is differently regulated from that in the kidney, and particularly that it is not profoundly affected by changes in the level of circulating angiotensin II. 4. An increase in renin mRNA was observed in the adrenal glands of the 'chronic' Goldblatt rats, which may be of relevance to the maintenance of hypertension in this model.
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PMID:Renal and extra-renal levels of renin mRNA in experimental hypertension. 185 Oct 70

In Goldblatt rats, the kidney exposed to high blood pressure reveals glomerulosclerosis. Moreover, in preexisting parenchymal renal disease, the development of glomerulosclerosis is accelerated in the unclipped kidney. Up to now, the pathogenetic mechanism underlying the development of glomerulosclerosis due to systemic hypertension has not completely been resolved. Traditionally, hemodynamic mechanisms have been discussed. This study was performed to investigate whether there might be a decreased activity of glomerular proteinases in the unclipped kidney of Goldblatt rats as a potential pathogenetic factor for glomerulosclerosis. 20 weeks after the surgical intervention, we found a reduced proteinase activity in ultrasonically destroyed isolated glomeruli obtained by differential sieving technique in comparison with the contralateral clipped kidney and the kidneys of sham-operated normotensive controls. This could be confirmed, when proteinase activity was related to DNA instead of protein. When investigating glomerular cathepsin B-content, a lysosomal enzyme, which is able to degrade glomerular structural as well as non-structural proteins, we found a decreased level in the kidney of Goldblatt rats exposed to systemic hypertension in comparison with normotensive control animals. Basing on these results we presume that glomerular protein accumulation and concomitant glomerulosclerosis due to systemic hypertension might be a result of a synergistical interaction between hemodynamic factors and biochemical ones; we suggest one of the latter to be a decreased glomerular proteinase activity.
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PMID:Proteinase activity in isolated glomeruli of Goldblatt hypertensive rats. 189 9

We investigated the structure and reactivity of small resistance arteries of two-kidney, one-clip (2K,1C) and one-kidney, one-clip (1K,1C) Goldblatt hypertensive rats within 4-6 wk of development of hypertension. Blood vessels from the mesenteric vascular bed with lumen diameter less than 300 microns were mounted on a wire myograph. The media of the vessel wall was significantly increased and lumen diameter was decreased in 2K,1C and 1K,1C rats. External diameter of blood vessels was reduced in both 2K,1C and 1K,1C rats, whereas cross-sectional area of the wall was increased significantly in 1K,1C rats. Wall tension in response to KCl was significantly lower in 2K,1C and 1K,1C hypertensive rats, whereas tension in response to norepinephrine (NE) was reduced in 1K,1C hypertensive rats but was similar in 2K,1C rats and controls. Active tension in response to arginine vasopressin (AVP) was similar in all groups. As a consequence of the reduced lumen circumference of small arteries, effective pressure in response to NE was similar in hypertensive and control rats, whereas effective pressure in response to AVP was exaggerated in the hypertensive rats. The sensitivity to NE and AVP was similar in all groups. These results show the rapid development of functional and structural changes in small resistance arteries in renal hypertensive rats within 4-6 wk of hypertension, with significant reduction in external and lumen diameters, increased media width, and increased media-to-lumen ratio, which enhance vascular reactivity to vasoconstrictors, in particular NE and AVP.
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PMID:Morphological and functional alterations of mesenteric small resistance arteries in early renal hypertension in rats. 192 99

Morphologic evidence from patients with essential hypertension and Goldblatt-type hypertension reveals a subpopulation of narrowed afferent arterioles to ischemic nephrons. These ischemic nephrons, responding individually to their perception of underperfusion, secrete renin. In response, the normal nephrons are in adaptive natriuresis and have appropriately shut off their renin production. Nevertheless, they are affected adversely by the discordant renin-angiotensin II arising from the ischemic nephrons' presence, which exerts an unwanted sodium-retaining effect on the proximal tubules of the adapting nephrons. The end result is elevated blood pressure from too much sodium retention for the level of renin activity, that is, an abnormal renin-sodium product. Thus, "normal" renin levels in a hypertensive individual are abnormal because healthy kidneys shut off renin production entirely when blood pressure rises. This construction explains why angiotensin converting enzyme inhibition often corrects "normal" renin hypertension. Although such hypertension may be partly sodium-mediated as a consequence of inappropriate sodium retention by the normal and ischemic nephrons, the source of the problem lies in the renin production from ischemic nephrons. The correct treatment, then, is an antirenin therapy designed to block renin synthesis or secretion or angiotensin II formation or action. In view of modern studies suggesting that renin excesses also correlate with an increased risk of heart attack and stroke, the role of antirenin and antiangiotensin agents in treatment assumes additional relevance.
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PMID:Discordant nephron function. A pathogenic factor in hypertension and its vascular complications of stroke and heart attack. 200 43

Hypertension is an established risk factor for atherosclerosis, a disease that is important in the pathophysiology of vein graft failure. Hypertension can also alter arterial vasoreactivity. The vasomotor function and histologic characteristics of autogenous vein grafts in hypertensive rabbits were assessed in this study. Hypertension was induced in 13 male New Zealand white rabbits by use of the Goldblatt one clip two kidney method. The right carotid artery was divided and bypassed with the reversed right external jugular vein 7 days later in these animals and in 13 normotensive controls. Blood pressure and renal function were assessed serially, and all the grafts were harvested after 28 days. Three grafts in each group were examined by light microscopy. The responses of the remaining grafts to norepinephrine, histamine, serotonin, and angiotensin II were determined in vitro under isometric tension. Endothelium-dependent relaxation to acetylcholine and calcium ionophore (A23187) was assessed in precontracted grafts. The mean arterial pressure was significantly increased after the Goldblatt procedure was performed. Intimal hyperplasia was observed in both groups, but the grafts in the hypertensive groups showed increased adventitial and medial fibrosis and a reduced number of vasa vasora. The grafts in the hypertensive rabbits were hypersensitive to all agonists as indicated by a significant reduction in their median effective dose values, and their maximal responses to all agonists were also significantly reduced. No graft relaxed in response to acetylcholine, and whereas precontracted grafts in normotensive rabbits had a maximal relaxation of 24% +/- 6% of precontraction with A23187, this was absent in the grafts in the hypertensive rabbits. The results suggest that angiotensin-induced hypertension may adversely affect vein graft patency by inducing hypersensitivity to physiologically important agonists and reducing the effect of receptor-independent endothelium-derived relaxation on vasomotor tone.
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PMID:Systemic hypertension alters vasomotor function in experimental vein grafts. 206 58

To assess the potential role of the lipoxygenase (LO) pathway in the vasculature in an angiotensin II (ANG II)-dependent model of hypertension, we investigated the effect of LO pathway inhibition on blood pressure in the two-kidney, one-clip (2K,1C) Goldblatt hypertensive rat. The development of renovascular hypertension in 2K,1C rats was attenuated by oral administration of phenidone (Phe, 60 mg.kg-1.day-1), a nonselective LO inhibitor, throughout the 3 wk of observation after renal artery constriction. In contrast, the same treatment protocol had no effect on the evolution of hypertension in the deoxycorticosterone acetate-salt rat, which is considered to be an ANG II-independent form of hypertension. The hypotensive effect of Phe was not associated with changes in plasma renin or aldosterone concentration (PRC and PAC, respectively). In vitro synthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) by aortic segments was increased in 2K,1C hypertensive rats compared with sham-operated rats. In addition, the synthesis of 12-HETE was suppressed by the in vitro addition of Phe (10(-4) M) to aortic-segment incubates obtained from 2K,1C rats and sham-operated rats. Acute administration of Phe (30 or 60 mg/kg) in 2K,1C hypertensive rats produced a rapid and sustained decrease in mean blood pressure (MBP). This decrease in MBP was accompanied by a brisk rise in PRC and PAC. In contrast, bolus administration of indomethacin, a selective cyclooxygenase inhibitor, did not affect MBP, PRC, or PAC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of lipoxygenase pathway reduces blood pressure in renovascular hypertensive rats. 212 26

The purpose of this study was to determine if hypertrophied myocardium was associated with diminished cardiac function, restricted oxygen supply, or oxygen consumption during tachycardia. Myocardial oxygen supply and oxygen consumption were determined during baseline and atrial pacing conditions 30 days after New Zealand White rabbits were prepared as one-kidney, one clip Goldblatt hypertensive or uninephrectomized sham control rabbits. Coronary blood flow and cardiac output, using radioactive microspheres, and small vessel oxygen saturations, using microspectrophotometry, were measured in hypertrophied and nonhypertrophied hearts. After 30 days, baseline blood pressure was significantly higher in the Goldblatt rabbits compared with sham controls, and hypertension was maintained during pacing. The myocardium was hypertrophied in the Goldblatt hypertensive rabbits compared with sham controls. Baseline heart rates were not different between animal groups (242 +/- 32 and 244 +/- 24 beats/min, respectively). Both groups were paced 35% above baseline heart rates; during pacing, cardiac output was similar to baseline values in the sham controls (304 +/- 99 versus 321 +/- 116 ml/min, respectively) but reduced in the hypertensive rabbits (248 +/- 43 versus 325 +/- 62 ml/min). Myocardial oxygen consumption increased twofold in both nonhypertrophied and hypertrophied ventricles during tachycardia. Oxygen extraction was significantly elevated, but coronary blood flow was not altered during pacing in either animal group. Therefore, at the pacing level chosen the diminished function in cardiac hypertrophy was not associated with reduced oxygen consumption. Conversely, reduced efficiency during pacing in the hypertrophied myocardium was suggested.
Hypertension 1990 Jul
PMID:Hypertension-induced cardiac hypertrophy. Oxygen supply and consumption with pacing. 214 26

The renal actions of atriopeptin III were compared in sham control, spontaneous and Goldblatt (2-K 1-C) hypertensive rats. Atriopeptin III, administered at 125. 250 and 500 ng/kg or 1.0, 1.5 and 2.0 micrograms/kg, into sham control rats had no effect on blood pressure or renal haemodynamics but caused dose related increases in urine flow, absolute and fractional sodium excretions, from 44 to 248%. Similar excretory responses to this dose range of atriopeptin III were obtained in spontaneously hypertensive rats. Atriopeptin III given at 125, 250 and 500 ng/kg into 2-K 1-C Goldblatt hypertensive rats increased reversibly left kidney urine flow, absolute and fractional sodium excretion by between 55 and 74% which were similar responses to those of sham control left kidneys. By contrast, atriopeptin III had much smaller effects on water and sodium excretions of the right clipped kidneys. These results suggest that atrial natriuretic peptides may be useful in mobilising fluid in genetic hypertension but their usefulness may be restricted in renovascular forms of hypertension.
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PMID:Renal actions of atriopeptin III in genetic and renovascular models of hypertension in the rat. 214 52


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