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)

Male Munich-Wistar rats were subjected to 1 2/3 nephrectomy. One group received no therapy (C). A second group received daily doses of methylprednisolone (MP). A third group received MP plus the angiotensin I converting enzyme inhibitor (CEI) benzazepril. A fourth group received CEI alone. Half of the rats in each group underwent micropuncture study 2 weeks after ablation. Untreated rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR), due to glomerular capillary hyperperfusion and hypertension. Administration of MP resulted in comparable systemic hypertension with further elevation of SNGFR due to even higher values for glomerular perfusion and hydraulic pressure (PGC). Concurrent treatment with CEI-controlled systemic and glomerular hypertension despite equivalent renal ablation and comparable doses of MP. After 12 weeks untreated rats demonstrated continued systemic hypertension, progressive proteinuria, and eventual glomerular sclerosis. Addition of MP dramatically accelerated the development of proteinuria and glomerular sclerosis, while CEI afforded striking protection against disease progression. Thus, potent vasodilator glucocorticoids may amplify hemodynamically mediated glomerular injury, whereas control of systemic and glomerular hypertension prevents this undesirable consequence of chronic steroid therapy.
 ...
PMID:Glucocorticoids amplify glomerular injury in rats with renal ablation. 337 Jan 34

We have recently developed a micropuncture technique to assess repeatedly function of the same nephrons in chronic renal disease and subsequently examine the morphology of their glomeruli by serial thin-section histological analysis. Using this approach, a potential causal linkage between early functional patterns and late structural abnormalities was examined in glomeruli of two established rat models of glomerular sclerosis. The models are (a) puromycin aminonucleoside (PAN) administration in unilaterally nephrectomized Munich-Wistar rats and (b) adriamycin (ADM) treatment in nonnephrectomized Munich-Wistar rats. Single nephron GFR (SNGFR) and glomerular capillary hydraulic pressure (PGC) were measured repeatedly for 8 (PAN rats) or 31 wk (ADM rats). In all animals studied, values for PGC remained at, or slightly below, levels measured before PAN or ADM administration. SNGFR values declined progressively in all glomeruli in PAN rats. Although some glomeruli in ADM rats had an increase in SNGFR above levels observed in nonnephrectomized control rats, these hyperfiltering glomeruli did not have abnormally high PGC nor did they exhibit glomerular sclerosis at the completion of the study. Histological analysis revealed the existence of a significant inverse correlation between the degree of sclerosis and SNGFR assessed at the time of sacrifice in both PAN and ADM groups. Chronic administration of captopril, an angiotensin I converting enzyme inhibitor, in PAN rats substantially attenuated development of glomerular sclerosis without affecting PGC in earlier stages. The observations in these models indicate that glomerular hyperfiltration and hypertension are not required for the development of glomerular sclerosis in renal diseases, and angiotensin I converting enzyme inhibitor can exert its protective effect independently of its effect on glomerular capillary pressure.
 ...
PMID:Serial micropuncture analysis of glomerular function in two rat models of glomerular sclerosis. 339 11

Male Munich-Wistar rats wer subjected to 1 2/3 nephrectomy. One group received no therapy. A second group received the angiotensin converting enzyme (ACE) inhibitor enalapril. A third group received triple therapy (TRX) with reserpine, hydralazine and hydrochlorothiazide. Half of the rats underwent micropuncture study 4 weeks after nephrectomy. Untreated rats exhibited high systemic blood pressure (SBP) and single-nephron hyperfiltration due to high values for the mean glomerular capillary hydraulic pressure (-PGC) and glomerular capillary plasma flow rate (QA). The ACE inhibitor therapy controlled both SBP and -PGC. In contrast, TRX normalized SBP but failed to lower -PGC. After 12 weeks untreated rats demonstrated systemic hypertension, progressive proteinuria and extensive glomerular sclerosis. The ACE inhibitor dramatically limited proteinuria and sclerosis. Despite equivalent SBP control with TRX, failure to control -PGC resulted in proteinuria and sclerosis comparable with the untreated rats. Thus unless -PGC is controlled, SBP control may be insufficient to prevent renal injury.
 ...
PMID:Antihypertensive therapy must control glomerular hypertension to limit glomerular injury. 355 75

We studied the glomerular hemodynamics and activity of the tubuloglomerular feedback system (TGFS) in Wistar rats with persistent hypertension 60 days after removal of the clipped kidney in the Goldblatt (two-kidney, one clip) hypertension model. Ten hypertensive rats (HBP) were compared with 12 normotensive ones (NBP). Micropuncture studies revealed that values for the single nephron glomerular filtration rate (SNGFR), glomerular plasma flow (QA), and afferent oncotic pressure (PAR.A) were similar in both groups, whereas glomerular capillary pressure (PGC) and effective filtration pressure (EFP) were higher in the HBP group (p less than 0.05). A slight but insignificant increase in afferent resistance was present in the HBP group. A positive correlation was found between mean arterial pressure and stop flow pressure (SFP) (r = 0.64, p less than 0.05) but not with SNGFR, suggesting a reduction in the ultrafiltration coefficient in hypertensive rats. This was further supported by studies of the activity of the TGFS, which demonstrated that interrupting flow to the macula densa was followed by a smaller increment in SNGFR in HBP, in spite of a similar rise in SFP. The mechanism responsible for decreasing glomerular permeability is unknown but could be related to structural changes in glomerular capillary or to an increase in intrarenal angiotensin II, as has been demonstrated previously in this model. It is suggested that these adaptations occurring in the kidney exposed to hypertension can contribute to the maintenance of elevated arterial pressure after removing the stenotic kidney.
Hypertension
PMID:Glomerular hemodynamics in persistent renovascular hypertension in the rat. 665 58

Micropuncture and/or morphologic studies were performed in seven groups of uninephrectomized (UNX) adult male Munich-Wistar rats. Control groups 1, 3, and 6 received standard (24% protein) chow and tap water. Groups 2, 4, and 5 received weekly injections of desoxycorticosterone pivilate (DOC) and 1% saline for drinking, groups 2 and 4 were fed standard chow, and Group 5 a diet containing 6% protein. Group 7 received DOC, salt, and standard chow for 3 wk followed by withdrawal of DOC and salt for an additional 6 wk. 10-14 d after UNX, groups 1 and 2 exhibited similar single nephron glomerular filtration rates (SNGFR) and initial glomerular plasma flow rates (QA). Group 2 had higher mean arterial pressure (AP) and glomerular capillary hydraulic pressure (PGC) than group 1. 3-4 wk after UNX, group 4 exhibited further elevations in AP and PGC as compared with groups 2 and 3. SNGFR and QA were similar in groups 3 and 4, but these average values were greater than typical for normal rats. Group 4 also demonstrated increased urinary protein excretion. Morphologic evaluation of glomeruli in groups 2 and 4 revealed mesangial expansion and focal intraglomerular hemorrhage whereas glomeruli of groups 1 and 3 were essentially normal. Values for AP and PGC in group 5 were not different than group 3 but significantly lower than group 4. QA and SNGFR were lower in group 5 (low protein) than in groups 3 and 4. Furthermore, proteinuria and glomerular structural lesions were abolished in group 5. Morphologic studies performed in groups 6 and 7 showed that early DOC-SALT lesions progress to focal glomerular sclerosis. These studies suggest that continued elevations in glomerular capillary flows and pressures predispose to glomerular injury in this model of systemic arterial hypertension.
 ...
PMID:Hemodynamic basis for glomerular injury in rats with desoxycorticosterone-salt hypertension. 671 46

Glomerular hemodynamics were studied of isolated perfused kidneys of 12-wk-old normotensive (NR) and spontaneously hypertensive (SHR) rats, using Pluronic F108 (BASF, Wyandotte, MI, USA) as a plasma expander. Glomerular filtration rate (GFR), proximal tubular hydrostatic pressure (PT) and glomerular capillary hydrostatic pressure (PGC) were approximately linearly related with renal perfusion pressure. PGC measured directly by micropuncture was comparable to PGC calculated from other parameters of glomerular dynamics using pore theory. We conclude that GFR in isolated kidneys perfused with Pluronic F108 is lower than in vivo, mainly as a result of an increase in PT. This rise in tubular pressure is due to an increased urine flow rate and an elevated tubular fluid viscosity. The difference in glomerular dynamics between NR and SHR kidneys is the result of an increased preglomerular vascular resistance in SHR, possibly due to an adaptive hypertrophic reaction to a sustained hypertension.
 ...
PMID:Glomerular filtration in the isolated perfused kidney. II. Glomerular hemodynamics. 686 20

These studies investigate glomerular hemodynamic responses to pregnancy in rats with 5/6th reduction of renal mass of four weeks duration. Both preglomerular and efferent arteriolar resistances (RA and RE) fell significantly at midterm although single nephron glomerular filtration rate (SNGFR) and glomerular plasma flow (QA) were unchanged versus virgins. In late pregnant rats with reduction of renal mass, the gestational fall in RA and RE was maintained and GFR, RPF, SNGFR and QA were higher compared to virgins. The gestational renal vasodilation was prolonged in this model of hypertension versus normals and a peripheral vasodilation is also indicated by the late fall in blood pressure. In virgins with 5/6th reduction of renal mass, PGC is elevated but in pregnant rats PGC fell towards term. The value of Kf was doubled in late pregnancy compared to virgins. All three groups of rats with reduction of renal mass showed similar proteinuria and similar levels of focal glomerular sclerosis, suggesting that pregnancy did not exacerbate the glomerular damage in this model of hypertension and renal disease. A decrease in hematocrit in late pregnancy compared with both virgin and midterm pregnancy indicated a plasma volume expansion. We conclude that when superimposed on hypertension with glomerular damage due to 5/6th reduction of renal mass, pregnancy induced gestational renal and peripheral vasodilation and plasma volume expansion. Since pregnancy was antihypertensive and lowered PGC, there was no hemodynamic basis for pregnancy-associated exacerbation of damage in this model of glomerular injury.
 ...
PMID:Glomerular hemodynamic responses to pregnancy in rats with severe reduction of renal mass. 756 89

This study was designed to determine whether glomerular hypertension develops as a function of age in the spontaneously hypertensive rat (SHR). Male SHR and age-matched Wistar-Kyoto (WKY) normotensive controls were divided into three groups for measurements of whole kidney and single nephron hemodynamics at 5, 10, and 15 months of age. As reported previously, SHR developed significant proteinuria which was predominantly an albuminuria, after 5 months of age. There were no differences in whole kidney or single nephron glomerular filtration rates between SHR and WKY. Afferent glomerular capillary hydraulic pressure (PGC) was slightly increased in SHR compared with WKY at 10 months of age. At 15 months of age, PGC in SHR was significantly lower than WKY. Our studies indicate that increased capillary pressure is not a major factor in the development and progression of renal injury in the spontaneously hypertensive rat.
 ...
PMID:Single nephron hemodynamics in spontaneously hypertensive rats. 777 Apr 70

Glomerular hyperfiltration has long been recognized in insulin-dependent diabetes, and has been more recently recognized in patients with non-insulin dependent diabetes mellitus as well. Experimentally, glomerular hyperfiltration has been shown to result from elevations in the glomerular capillary blood flow and the glomerular capillary hydraulic pressure (PGC). Of the hemodynamic determinants of hyperfiltration, it is glomerular hypertension that is most damaging to the glomerulus. Experimental and clinical studies have confirmed that antihypertensive agents that lower PGC more consistently slow the progression of injury than do those that fail to control glomerular hypertension. The pathogenesis of diabetic hyperfiltration is multifactoral. Many mediators have been proposed, including changes due to the altered metabolic milieu, and alterations in endogenous levels of such vasoactive mediators as atrial natriuretic peptide, endothelial-derived relaxing factor, angiotensin II, prostaglandins, thromboxanes, and kinins, among others. It has more recently been suggested that local renal tissue levels, rather than circulating levels, play the more profound role in hemodynamic regulation. For example, the renin-angiotensin system (RAS) appears to be disproportionately active in the renal tissue, potentially explaining the renal vascular responsiveness to angiotensin-converting enzyme inhibition despite absence of systemic RAS activation. Little is yet known of the mechanisms by which glomerular hypertension leads to injury. Innovative new in vitro systems have been developed to address this question. These studies postulate that glomerular hemodynamic factors (shear stress, pulsatile flow) modify the growth and activity of glomerular component cells, inducing the expression of cytokines and other mediators, which then stimulate matrix production and promote structural injury.
 ...
PMID:Current concepts of renal hemodynamics in diabetes. 857 53

Studies were conducted to investigate the impact of nitric oxide synthesis inhibition on blood pressure and glomerular hemodynamic adaptations to pregnancy in the rat. In normal pregnancy, urinary excretion of NO2 + NO3 (NOx), reflecting increased nitric oxide (NO) production, progressively increased. Blockade of NO production in virgin and late pregnant Sprague-Dawley rats caused systemic hypertension, increased renal vascular resistance (RVR), reductions in RPF but GFR remained unchanged. In cortical nephrons, preglomerular and efferent arteriolar resistance (RA and RE) were elevated and glomerular capillary blood pressure (PGC) increased markedly. Glomerular plasma flow (QA) and the glomerular capillary ultrafiltration coefficient, Kf, were reduced without change in single nephron glomerular filtration rate (SNGFR) because of the large elevation in PGC. The pressor and glomerular hemodynamic responses to NO blockade were similar in virgins and pregnancy. Urinary NOx excretion was markedly reduced in all groups with chronic NO blockade. Inhibition was incomplete in pregnancy, however, and a level of NO production that was adequate for normal BP and renal function in virgins, led to severe vasoconstriction in pregnancy. The present studies suggest that chronic NO deficiency leads to derangement of the hemodynamic adaptations of pregnancy.
 ...
PMID:Impact of nitric oxide deficiency on blood pressure and glomerular hemodynamic adaptations to pregnancy in the rat. 888 70


<< Previous 1 2 3 4 5 6 7 Next >>