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

The clearance of [131I]orthoiodohippurate and 99mTc-mercaptoacetyltriglycine provide a measure of effective renal plasma flow, yet these clearances are proportional to renal plasma flow only if the extraction fraction remains constant. To determine the effect of unilateral renal artery stenosis, captopril, renal ischemia, and partial renal vein occlusion on renal blood flow and the extraction fraction of [131I]orthoiodohippurate, 99mTc-mercaptoacetyltriglycine, and [125I]iothalamate, we conducted a series of constant infusion studies in Sprague-Dawley rats. Renal artery flow reduction of approximately 70% decreased the extraction fraction of all three agents (P < or = .05). Captopril had no effect on extraction fraction in controls, but it produced a further decrease in extraction fraction of 99mTc-mercaptoacetyltriglycine and [131I]orthoiodohippurate in rats with renal artery stenosis (P < or = .05). Ischemia resulted in a 16% decrease in flow (P < .01) but a much larger (47% to 65%) decrease in extraction fraction of all three agents (P < .002). Partial renal vein occlusion also decreased the extraction fraction of all three agents (P < or = .05). The changes in extraction fraction imply that the clearances of [131I]orthoiodohippurate and 99mTc-mercaptoacetyltriglycine in disease states may not be proportional to renal plasma flow. Furthermore, in rats with renal artery stenosis it appears that renal blood flow must fall below a critical threshold of approximately 58% before extraction fraction decreases; as renal blood flow is further reduced below this threshold, there is a corresponding reduction in extraction fraction (P < .01).
Hypertension 1994 Jan
PMID:Renal artery stenosis and ischemia. Effect on renal blood flow and extraction fraction. 828 36

Some reports have stated that central norepinephrine (NE) depletion inhibited the development of hypertension in the rat. On the other hand, this pharmacological treatment induces changes on the central renin-angiotensin system. The present study was designed to follow the development of 2 kidney-2 clip (2k-2c) renovascular hypertension in rats depleted of central NE and to analyze the central and peripheral renin-angiotensin system. Male Wistar rats (n = 40) were used. Half of the animals was injected, intracisternally, with 6-hydroxydopamine (6-OHDA), the remaining rats only received the vehicle. One week later a silver clip was placed on each renal artery on half of the 6-OHDA treated rats and on half of the vehicle treated animals. A sham operation was performed on the remaining rats. Blood pressure was measured weekly during 7 weeks. Then, blood and cerebrospinal fluid (CSF) samples were obtained. The brain was dissected in several areas. NE and angiotensinogen concentration (AoC) were determined in tissue samples. AoC was evaluated in plasma and CSF; plasma renin activity was also measured. Hypertension development was not prevented by central NE depletion, which was significant in all central areas (p < 0.001). Other significant results showed that renal ischemia and/or NE depletion induced a significant increase in angiotensinogen concentration in the hypothalamus (p < 0.01) and in CSF (p < 0.05). In summary: central NE depletion was not able to modify the development of 2 k - 2 c hypertension. Treatment and renal ischemia induced an increase of central AoC.
 ...
PMID:Effect of central norepinephrine depletion on renovascular hypertension and on the renin system. 837 8

In arterial hypertension associated with primary or secondary hyperaldosteronism myocardial fibrosis is an important determinant of pathologic hypertrophy. To further examine the relationship between elevations in plasma aldosterone (ALDO) and myocardial fibrosis, we analysed perivascular collagen area (PVCA) and interstitial collagen volume fraction (CVF) by videodensitometry and hydroxyproline concentration (HPro) by high-performance liquid chromatography. We examined both the left (LV) and right (RV) ventricles in the following rats models of primary or secondary hyperaldosteronism of eight weeks duration: unilateral renal ischemia (RHT); continuous ALDO administration via osmotic minipumps (0.75 microgram/h s.c.) and enhanced dietary sodium following uninephrectomy (AL); in RHT and AL after pre- and continuous treatment with either 20 (S) or 200 (SS) mg/kg/day s.c. of the aldosterone receptor antagonist, spironolactone; in AL after pre- and continuous treatment with 50 mg/kg/day oral captopril (AL + CAP); as well as in age and sex matched controls (C). Systolic arterial pressure was comparably elevated in RHT and AL (202 +/- 12 and 193 +/- 7 mmHg, respectively; P < 0.0005 vs C); it remained elevated with low dose spironolactone in either model of arterial hypertension, but was normalized with high dose spironolactone or captopril in AL. Left ventricular hypertrophy (LVH), expressed as significantly elevated LV/RV weight or LV/BW ratios, was present in all experimental groups, excluding AL + SS and AL + CAP, when compared with C (P < 0.005). In each ventricle, CVF and PVCA were increased (P < 0.005) in either model of hypertension and in AL + CAP, but were no different from C in all groups receiving either dose of spironolactone. Similar findings were observed for HPro. Thus, myocardial fibrosis was comparable in primary or secondary hyperaldosteronism, wherein elevations in plasma aldosterone, relative to increased sodium intake, are associated with arterial hypertension. The competitive ALDO receptor antagonist, spironolactone, was able to prevent fibrosis in either model irrespective of the development of LVH and the presence of hypertension. Captopril prevented hypertension and LVH, but not unexpectedly it did not prevent myocardial fibrosis in primary hyperaldosteronism. These findings provide further evidence that in these rat models increased plasma ALDO, relative to dietary sodium, plays a major role in the adverse accumulation of collagen that appears in the myocardium.
 ...
PMID:Anti-aldosterone treatment and the prevention of myocardial fibrosis in primary and secondary hyperaldosteronism. 837 16

The purpose of this study was to elucidate the role of endogenous angiotensin II in mediating the renovascular effects of renal adrenergic stimulation. Six conscious dogs instrumented for monitoring of renal blood flow were subjected to step increases every 10 minutes in the rate of norepinephrine infusion into the renal artery. Under control conditions, infusion of norepinephrine (10-40 ng/min per milliliter per minute of control renal blood flow) increased plasma renin activity and decreased renal blood flow progressively by approximately 10-75%. When increments in angiotensin II during norepinephrine infusion were abolished by fixing plasma levels of angiotensin II at either normal or high concentrations by chronic infusion of captopril plus angiotensin II, renal blood flow responses to adrenergic stimulation were greatly attenuated at rates of norepinephrine infusion that decreased renal blood flow up to approximately 40% under control conditions. Thus, acutely generated angiotensin II appeared to contribute to the renovascular effects of norepinephrine. However, when endogenous levels of angiotensin II were suppressed to low levels by chronic infusion of captopril alone, norepinephrine induced severe renal ischemia at much lower rates of infusion than occurred when the renin-angiotensin system was intact. Since this enhanced sensitivity to norepinephrine did not occur during chronic captopril infusion when angiotensin II was given simultaneously at rates that restored mean arterial pressure to normotensive levels or higher, low arterial pressure during chronic captopril administration may predispose the kidneys to excessive renal vasoconstriction during renal adrenergic stimulation.
Hypertension 1993 May
PMID:Influence of endogenous angiotensin on the renovascular response to norepinephrine. 849 4

In an effort to further evaluate the potential application of laparoscopy to urologic surgery, we explored the feasibility of using this minimally invasive approach for performing a partial nephrectomy. Nine female pigs underwent laparoscopic partial nephrectomy (LPN) utilizing a plastic cable tie (15 mm. x 4 mm. x 1 mm.) to achieve renal ischemia and an Argon Beam Coagulator probe (ABC) (Birtcher Medical Systems) to fulgurate the transected surface. Six weeks after LPN, 6 pigs underwent creatinine clearance, renin level, arteriography, BP samples and were then killed. The renal remnants were weighed and sectioned for histological studies. These studies revealed excellent function of the renal remnant, no AV fistula, and no evidence of renovascular hypertension. LPN is a feasible, repeatable procedure in the pig. Control of the renal hilum, transient parenchymal compression with a plastic cable, and use of the argon beam coagulator are key elements in performing this procedure.
 ...
PMID:Laparoscopic partial nephrectomy in the pig model. 1143 70

A growing body of evidence supports the notion that calcium antagonists exert a renal protective effect. Calcium antagonists may play an important future role in renal hemodynamics related to their reversal of renal vasoconstrictors. Calcium antagonists are also capable of blocking intracellular calcium overload induced by various types of ischemia or toxic stimuli. Features such as these may be of substantial value in ameliorating acute renal insufficiency secondary to renal ischemia, iodinated radiographic contrast media, or the administration of various nephrotoxic drugs. The latter includes agents such as the aminoglycoside antibiotics, cyclosporine A, and the cancer chemotherapeutic agent cisplatin. Recent prospective, controlled studies from our group indicate that calcium antagonists protected against postischemic acute renal failure in the setting of cadaveric renal transplantation. Moreover, in a prospective, randomized, controlled clinical trial, we were able to demonstrate that the prophylactic use of nitrendipine reduced the decrease in GFR in patients receiving radiographic contrast agents. Such protection may extend to favorably influencing the course of chronic renal insufficiency, particularly when the latter is complicated by hypertension. Seven putative mechanisms have been proposed by which calcium antagonists may ameliorate the decline in GFR associated with renal insufficiency. These are: (a) reduction in blood pressure per se, (b) reduction in renal hypertrophy, (c) modulation of mesangial traffic of macromolecules, (d) reduction in metabolic activity in remnant renal tissue, (e) amelioration of uremic nephrocalcinosis, (f) reduction of pressure-induced calcium entry into vessel walls, and (g) reduction of free radical formation. Experimental investigations in rats with reduced renal mass, desoxycorticosterone-induced hypertension, or chronic angiotensin II infusion, and in spontaneously hypertensive rats support such a view.
 ...
PMID:Calcium antagonists and renal protection. 851 90

Blood pressure increases with age in all US population groups that have been studies, but does so faster in African Americans. Evidence from extensive microscopic renal vascular studies at autopsy supports the view that blood pressure increases with age because of progressive fibroplasia of renal interlobular arteries and arterioles that leads to incrementally escalating renal ischemia. This process precedes the development of hypertension and progresses, on average, faster in African Americans compared with whites. The etiology for fibroplasia of the renal vasculature and the reasons for its faster progression in African Americans remains unknown.
 ...
PMID:Renovasculopathies of hypertension and the rise of blood pressure with age in blacks and whites. 866 60

A case of thrombotic microangiopathy presenting as a hemolytic uremic syndrome complicated by untreatable hypertension and ultimately requiring bilateral nephrectomy is discussed. Severe hypertension and renal failure may complicate the course of vascular diseases of the kidney, including thrombotic microangiopathy, chronic hypertension, and scleroderma. Toxins, pressure stress, and immune material may trigger the initial injury to vascular endothelium. The malignant course of these renal vascular diseases seems linked to the severity of vascular injury. Endothelial injury manifests with swelling and detachment of endothelial cells from the basement membrane, expansion of the subendothelial space, and newly formed basement membrane-like material. In arterioles, endothelial injury precedes myointimal swelling and proliferation, leading to vascular lumina narrowing or obliteration and secondary glomerular ischemia, with glomerular tuft collapse and garland-like wrinkling and thickening of the capillary wall. Endothelial cell injury is very likely the common determinant of a cascade of events that lead to irreversible renal failure. When the initial insult (toxins, mechanical stress, antibodies) is promptly removed, lesions are self-limiting and the patient usually recovers. However, a severe insult persisting for some time can lead to chronic and irreversible vascular lesions that, through renal ischemia, trigger maximal activation of the renin angiotensin system with a brisk elevation in arterial blood pressure that may combine to further vascular injury and renal ischemia. Moreover, enhanced shear stress in the severely narrowed microcirculation, through abnormal von Willebrand factor processing, can also favor endothelial injury and platelet aggregation, which may further worsen the vascular lesions and sustain the microangiopathic process. Plasma manipulation, arteriolar vasodilators, and angiotensin-converting enzyme inhibitors normally control the vicious circle, but in few severe cases bilateral nephrectomy remains the last chance to save the patient's life.
 ...
PMID:Malignant vascular disease of the kidney: nature of the lesions, mediators of disease progression, and the case for bilateral nephrectomy. 867 55

Thus I would like to conclude by saying that an idiopathic form of obliterative renal arteriopathy account for the rare presentation of severe hypertension and progressive renal failure with or without overt hemolytic anemia and thrombocytopenia in children. It can be labelled as primary malignant nephrosclerosis (NScl) or atypical HUS, based on primary thrombotic angiopathy. This, essentially intimal changes, is seen in diverse conditions and appears to result from primary endothelial injury followed by intimal exudation, thrombosis, and repair by fibrosis. Persistent or recurrence of this process form the basis of progressive obliterative arteriopathy. The result is renal ischemia and renin-angiotensin mediated hypertension. Establishment of a vicious circle would further accelerate HT and lead to end stage renal failure. Early recognition and prompt therapeutic intervention might prove beneficial.
 ...
PMID:Thrombotic microangiopathy with hypertension and acute renal failure in children (a typical hemolytic uremic syndrome). 869 75

Approximately 15% of end-stage renal disease is attributable to chronic ischemic nephropathy from renovascular disease, representing significant patient morbidity and sizable medical costs. Although the pathophysiology of both ischemic acute renal failure and renovascular hypertension are under intense study, there have been little data obtained on the pathophysiology of chronic ischemic injury to the kidney. Data from studies of renovascular hypertension demonstrate the primary dependence of the stenotic kidney on angiotensin II in maintenance of glomerular filtration rate, although other vascular regulators, such as endothelium-derived nitric oxide and endothelin, may also play a role. Clues to the pathophysiology of cellular injury in chronic ischemic nephropathy can be found in acute models of ischemic injury to the tubules, toxic models of chronic decreased blood flow such as cyclosporine, and from recent pathological studies showing immunologic alterations. Because there are very little data on the cellular mechanisms of chronic ischemic injury to the kidney, this is an important area for laboratory investigation, particularly because the techniques developed both in studies of acute renal ischemia and chronic renovascular hypertension are readily available. Further understanding of the cellular mechanisms of chronic renal ischemia may eventually lead to medical interventions for patients with ischemic nephropathy too ill to undergo major abdominal surgery.
 ...
PMID:Cellular and metabolic consequences of chronic ischemia on kidney function. 872 84


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>