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)

MK-0521 and captopril were orally administered to acute (6 to 8 days after unilateral renal artery constriction) and chronic (2 to 2.5 months after the constriction) 2-kidney Goldblatt hypertensive dogs for 7 to 21 days. MK-0521 lowered the blood pressure to similar extents in the acute and chronic stages of hypertension. The antihypertensive effect of MK-0521 was dose-dependent and persistent even after its cessation. Captopril also produced an antihypertensive effect, although the effect in the chronic stage of hypertension was less prominent than that in the acute stage of hypertension. MK-0521 was more inhibitory on the renin-angiotensin system than captopril. In the acute stage of hypertension, the dogs treated with MK-0521 had increased angiotensin converting enzyme (ACE) activity, while they had decreased plasma angiotensin II level and elevated plasma angiotensin I level and plasma renin activity. These results clarified the inhibitory effect of MK-0521 on ACE. In contrast, in the chronic stage of hypertension, MK-0521 showed no depression of plasma angiotensin II. There were no significant changes in daily urinary volume, and renal clearances of sodium, potassium and creatinine. These results suggest that the major mechanism of the antihypertensive effect of MK-0521 in 2-kidney Goldblatt hypertensive dogs is an inhibition of the ACE. In addition, the different effects in the acute and chronic hypertensive dogs suggest that some differences exist in the mechanisms of maintaining blood pressure between the two stages of 2-kidney Goldblatt hypertensive dogs.
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PMID:[Antihypertensive effect of repeated oral administration of MK-0521 in 2-kidney Goldblatt hypertensive dogs]. 254 80

The effects of renovascular hypertension and its treatment by a converting enzyme inhibitor (perindopril) on the structure and function of large arteries were studied in the Goldblatt 1 clip--2 kidney rat. One month after the surgical operation, the hypertensive animals (n = 24) and the sham operated animals (n = 24) were divided into two groups receiving either 1 mg/kg per day of perindopril or distilled water for four weeks. At the end of treatment, the hemodynamic parameters, including blood pressure and instantaneous blood flow measured by Doppler, were measured in anesthetized rats. The mechanical properties of the carotid artery were studied by in situ measurement of the carotid compliance in response to imposed pressures. Lastly, morphometric parameters of the thoracic aorta, including the thickness of the media, the density of elastin, collagen and nuclei and the area of the nuclei were studied by an automated image analysis system. Hypertension was associated with an increase in the characteristic impedance of the aorta (14,479 +/- 5,171 vs 9,022 +/- 4,071 dyne.sec/cm5; p less than 0.01) and a reduction in systemic arterial compliance (2.41 +/- 0.96 vs 3.92 +/- 1.15 x 10(-3) ml/mmHg; p less than 0.01) or carotid arterial compliance (6.31 +/- 1.85 vs 8.38 +/- 3.14 x 10(-2) mm3/mmHg; p less than 0.05). Treatment with perindopril normalized systolic and diastolic blood pressure and completely inverted the markers of rigidity of the large arteries. Morphometric analysis of the aortic wall allowed these functional modifications to be attributed to structural modifications of the wall. The thickness of the media was increased by hypertension (122.3 +/- 3.7 vs 97.5 +/- 4.4 microns; p less than 0.01). This thickening was attributed to hypertrophy of the smooth muscle cells as evidenced by the increase in the nucleus size (8.58 +/- 1.54 vs 7.38 +/- 0.78 microns 2; p less than 0.01). It was accompanied by an increase in the density of collagen (8.6 +/- 3.6 vs 7.3 +/- 2.4%; p less than 0.01) and a decrease in the density of elastin (31.9 +/- 8.3 vs 38.6 +/- 12.8%; p less than 0.01). Treatment with perindopril normalized the thickness of the media (103.0 +/- 4.8 microns) by reducing cellular hypertrophy. The short duration of treatment did not allow regression of the modifications in the density of the proteins of the interstitial matrix. In conclusion, renovascular hypertension severely alters the functional and structural properties of large arteries. Treatment with perindopril normalizes the properties of the vessel wall.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of chronic converting enzyme inhibition on the structure and function of large arteries in the rat. 260 98

The effects of dietary K (food and tap water both containing 1% KCl) on blood pressure and renal prostaglandin-kallikrein-kinin system were investigated in Wistar rats made hypertensive by constriction of left renal artery. Dietary K attenuated the development of hypertension and increased urine volume accompanied by increased excretion of K, but by uninfluenced excretion of Na. Dietary K also increased the urinary excretion of kallikrein, PGE2 and aldosterone in Goldblatt hypertensive rats. There was no significant difference in the values of plasma Na between the two groups with and without dietary K. These results suggest that dietary K may attenuate the development of hypertension, increase urine volume via the mechanism of enhancing production of renal PGE2 and kallikrein in hypertensive rats.
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PMID:[Effects of dietary K on blood pressure, prostaglandin, and kallikrein in renovascular hypertensive rats]. 261 29

The cause and mechanism of post-carotid endarterectomy hypertension remains unknown. To determine the influence of the sympathetic and renin-angiotensin system, we measured cranial and peripheral plasma levels of catecholamine and renin in patients undergoing carotid endarterectomy. Baseline samples were drawn just before carotid clamping (sample I) and compared with study samples drawn immediately after clamp release (sample II), 2 to 6 hours after surgery (sample III), and then 18 to 24 hours after surgery (sample IV). The patients with post-carotid endarterectomy hypertension had an associated increase of cranial and peripheral norepinephrine levels in the postoperative hypertensive period whereas the patients without post-carotid endarterectomy hypertension did not. This association was most pronounced and statistically significant in cranial samples II (p = 0.032) and III (p = 0.005). Epinephrine and dopamine values did not correlate with post-carotid endarterectomy hypertension. Renin values were higher in cranial than in peripheral samples at time period 2 (p = 0.011), suggestive of a central nervous system Goldblatt phenomenon. However, the renin values did not correlate with post-carotid endarterectomy hypertension. We conclude that post-carotid endarterectomy hypertension is associated with elevated cranial norepinephrine levels, suggestive of a central nervous system sympathomimetic mechanism. Optimal prevention and treatment of this brief but frequently occurring hypertension should include a central-acting sympatholytic agent.
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PMID:Post-carotid endarterectomy hypertension: association with elevated cranial norepinephrine. 264 44

The effect of clipping the left renal artery on left and right kidney renin mRNA levels during the early and chronic phases of two-kidney, one clip Goldblatt hypertension in the rat was studied. Renin mRNA levels were determined using northern and dot blotting. Four weeks after clipping, renin mRNA levels were sixfold higher in the left kidney and eightfold lower in the right kidney of the Goldblatt rats compared with the left kidney of the sham-operated rats. Similar analysis at 20 weeks after clipping showed a fourfold increase in the left kidney and a 16-fold suppression in the right kidney compared with age-matched sham-operated control rats. The study demonstrates the profound changes that occur in renin gene expression in the clipped and contralateral kidneys in this model of hypertension and shows that these changes persist into the chronic phase of the hypertension.
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PMID:Kidney renin mRNA levels in the early and chronic phases of two-kidney, one clip hypertension in the rat. 264 44

Renal failure is progressive irrespective of the underlying primary renal disease or continued disease activity. Intrarenal haemodynamic changes may contribute to progressive loss of renal function, and may be modified by pharmacological therapies. Angiotensin-converting enzyme (ACE) inhibitors may have a specific therapeutic advantage in the treatment of hypertension associated with progressive renal disease. We have studied the effects of an ACE inhibitor and a calcium channel blocker on systemic BP, glomerular filtration, proteinuria and histological injury in animal models of progressive renal disease (the remnant kidney and diabetes). Systemic BP was lowered similarly by each treatment in both models. Beneficial effects on renal structure, proteinuria, and glomerular filtration only occurred in the ACE inhibitor-treated animals. Intrarenal haemodynamic effects of ACE inhibitors may therefore offer an advantage over other antihypertensive agents in progressive renal disease. Where there is reduced renal perfusion, intrarenal haemodynamic effects of ACE inhibitors may lead to compromised renal function. Acute renal failure is a common consequence of ACE inhibitor therapy in patients with bilateral renal artery stenosis, or renal artery stenosis to a single functioning kidney. Acute studies have suggested that these effects are reversible; function returns following withdrawal of ACE inhibitor therapy. We examined the long-term effects of ACE inhibitor therapy in rats with the two-kidney, one-clip (Goldblatt) model of hypertension. Rats were treated for 12 months with an ACE inhibitor or a vasodilator. After 1 year of treatment the clipped kidney from the ACE inhibitor-treated rats was small, fibrotic, and had no glomerular filtration. No functional improvement of the clipped kidney occurred following ACE inhibitor withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin-converting enzyme inhibition in renal disease; contrasting effects on renal function in renal artery stenosis and progressive renal injury. 267 36

In order to investigate the peripheral neuroeffector functions of renal hypertension, norepinephrine release from the sympathetic nerve endings and vascular responsiveness were evaluated in the mesenteric vasculatures from two-kidney, one-clip Goldblatt hypertensive rats (2K, 1C-HT). Norepinephrine release and pressor responses during periarterial nerve stimulation (40 V, 5 msec rectangular pulses for 1 min, 5, 10 and 15 Hz) were unchanged during the acute phase (3 weeks after surgery), and were rather reduced during the chronic phase (7-8 weeks after surgery) in 2K, 1C-HT compared to sham-operated normotensive control rats. By contrast, the vasoconstrictor responses to exogenously applied norepinephrine were significantly greater in 2K, 1C-HT than in the normotensive controls. From these observations, it seems unlikely that peripheral adrenergic function in the blood vessels plays an important role in the pathogenesis of 2K, 1C-HT. However, the increased sensitivity of vascular smooth muscle cells to norepinephrine may contribute to the maintenance of high blood pressure in the face of reduced vascular sympathetic tone in this form of hypertension.
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PMID:Neurotransmitter release and vascular responsiveness in mesenteric vasculatures from two-kidney, one-clip Goldblatt hypertensive rats. 272 32

Experimental renovascular malignant arterial hypertension was produced by modified Goldblatt's procedures, in 60 rhesus monkeys, and various retinal arteriolar changes in hypertensive retinopathy were studied in detail (by serial ophthalmoscopy, and stereoscopic color fundus photography and fluorescein fundus angiography on long-term follow-up). The retinal arteriolar changes, in ophthalmoscopically visible arterioles, consisted of arteriolar sclerosis and associated changes, e.g., increased arteriolar tortuosity, arteriolar narrowing and in some animals occlusion and sheathing of the fine arterioles; we could find no evidence of localized or generalized 'spasm' in these retinal arterioles. Eyes in animals with accelerated arterial hypertension revealed focal dilatation and leakage of the retinal precapillary terminal arterioles (resulting in development of focal intraretinal periarteriolar transudates), and also occlusion of the terminal retinal arterioles (producing cotton-wool spots and associated intraretinal microvascular abnormalities). We discuss the controversial subjects of narrowing (particularly 'spasm') of ophthalmoscopically visible retinal arterioles and of fibrinoid necrosis in malignant hypertension.
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PMID:Retinal arteriolar changes in malignant arterial hypertension. 274 97

We produced experimental renovascular malignant arterial hypertension by modified Goldblatt's procedures, in 60 rhesus monkeys. Hypertensive retinopathy was studied in detail (by ophthalmoscopy, and stereoscopic color fundus photography and fluorescein fundus angiography on long-term follow-up). Cotton-wool spots (CWSs) were found to be an important, early retinal lesion. On ophthalmoscopy, they had a characteristic appearance. Fluorescein fundus angiography of these lesions revealed focal retinal capillary nonperfusion. The CWSs usually lasted for over 3 weeks and resolved within 6 weeks, leaving permanent obliteration of the retinal capillaries in their distribution, secondary intraretinal microvascular abnormalities, and retinal nerve fiber loss. We discuss pathogenesis and other features of CWSs. There is overwhelming evidence that CWSs are due to occlusion of the terminal retinal arterioles, resulting in acute focal inner retinal ischemia; hence the scientifically valid term for them would be 'inner retinal ischemic spots'.
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PMID:Cotton-wool spots (inner retinal ischemic spots) in malignant arterial hypertension. 274 98

We produced experimental renovascular malignant arterial hypertension by a modified Goldblatt's procedure in 60 rhesus monkeys (25 one-kidney model and 35 two-kidney model), and studied various macular lesions by detailed serial ophthalmoscopy, and stereoscopic color fundus photography and fluorescein fundus angiography on a long-term follow-up. The various lesions which developed in the macular region included retinal edema, cystic retinal changes, serous retinal detachment, retinal pigment epithelial changes (initially acute focal and later degenerative lesions), and lipid deposits. In addition to these, the usual retinal lesions associated with hypertensive retinopathy, e.g., focal intraretinal periarteriolar transudates, cotton-wool spots and retinal hemorrhages, were also frequently seen in the macular retina. Findings on the various lesions are described in detail, and the pathogenesis of macular edema in malignant arterial hypertension is discussed.
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PMID:Macular lesions in malignant arterial hypertension. 274


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