Biomedical subjects

R J Roman

Publications and source records attributed to R J Roman.

At least 127 records · Page 7Linked to original sources

PubMed1992

Mesangial cell immune injury. Hemodynamic role of leukocyte- and platelet-derived eicosanoids.

The role of leukocytes and platelets and of leukocyte- and platelet-derived eicosanoids in mediating acute changes in renal and glomerular hemodynamics was assessed in a model of antibody-induced mesangial cell injury in the rat. After a single intravenous injection (6 mg/kg) of the monoclonal antibody (ER4) against the mesangial cell membrane antigen Thy 1, significant decrements in glomerular filtration rate (GFR) and renal blood flow (RBF) were observed at 1 h, and were associated with increments in glomerular LC (+) leukocyte counts and in the synthesis of thromboxane (Tx)B2, leukotriene (LT)B4, and 12-hydroxyeicosatetraenoic acid (HETE). In rats with immune leukopenia, the rise in glomerular LC (+) leukocytes and in eicosanoid synthesis were abolished and the fall in GFR and RBF after administration of ER4 were completely ameliorated. Likewise, pretreatment of rats with both a thromboxane synthase and a 5-lipoxygenase inhibitor also blocked the fall in GFR and RBF and the rise in glomerular synthesis of TxB2 and LTB4 produced by ER4 without changing glomerular LC (+) leukocyte counts. Selective inhibition of thromboxane or 5-lipoxygenase alone only partially ameliorated the decrements in GFR and RBF produced by ER4. In animals with immune thrombocytopenia, the elevated glomerular synthesis of 12-HETE and fall in RBF but not GFR was ameliorated after administration of ER4. The ER4 antibody-induced fall in GFR was mainly caused by a marked decrement in the ultrafiltration coefficient, Kf, which was dependent on TxA2 and 5-lipoxygenase products, since pretreatment of animals with a thromboxane receptor antagonist or with a 5-lipoxygenase inhibitor partially ameliorated this decrement. Structural changes such as infiltration of glomerular capillaries by leukocytes and endothelial cell damage may also have accounted for the fall in Kf. These observations indicate that in antibody-mediated mesangial cell injury, infiltrating leukocytes and platelets mediate the changes in renal hemodynamics via synthesis of thromboxane and arachidonate 5-lipoxygenation products.

Animals↗

PubMed1992

Genetic heterogeneity and differences in glomerular hemodynamics between inbred colonies of Munich-Wistar rats.

DNA fingerprint analysis and renal micropuncture studies were performed in Munich-Wistar rats purchased from Harlan Industries and Simonsen Laboratories to determine whether these rats are genetically heterogeneous and exhibit differences in glomerular hemodynamics. RBF and GFR were similar in rats from both colonies. Glomerular capillary pressure was lower in rats from the Harlan colony (46 +/- 2 mm Hg) than in those from the Simonsen colony (56 +/- 2 mm Hg). The low glomerular capillary pressure in the Harlan rats was primarily due to a lower postglomerular vascular resistance. The estimated whole-kidney ultrafiltration coefficient (Kf) was significantly greater in the rats obtained from the Harlan colony than in those obtained from the Simonsen colony (0.12 +/- 0.03 versus 0.05 +/- 0.01 mL/min/g kidney wt/mm Hg). The DNA fingerprints of the Simonsen rats were different from those of the Harlan rats. These results provide evidence of physiologic and genetic heterogeneity between commercially available inbred strains of Munich-Wistar rats in the United States and suggest that comparison of results with Munich-Wistar rats from different sources may be more difficult than previously recognized.

Adrenal Glands↗

PubMed1992

Effect of renal medullary circulation on arterial pressure.

PRESSURE-NATRIURESIS EFFECTS IN HYPERTENSION: Considerable advances have been made in our understanding of pressure-natriuresis and the effects of this mechanism in hypertension. We have shown that in the absence of changes in neural and endocrine factors, sodium and water excretion doubled when arterial pressure was increased by only 10 mmHg. These responses were greatly blunted or obscured by elevations in renal sympathetic tone, infusion of the vasoconstrictors angiotensin and vasopressin or by inhibition of paracrine factors such as eicosanoids and nitric oxide. EFFECT OF CHANGES ON MEDULLARY BLOOD FLOW: The pressure-natriuresis response is closely associated with changes in papillary blood flow as determined by laser-Doppler flowmetry. In volume-expanded rats, papillary blood flow is not well autoregulated, which results in elevations of vasa recta capillary pressure and renal interstitial fluid pressure. The increased interstitial fluid pressure is transmitted from the medulla to the cortex in the encapsulated organ and is associated with inhibition of sodium transport in the proximal tubule and/or the thin descending loop of Henle of deep nephrons. Selective reductions in medullary blood flow by infusion of the nitric oxide inhibitor N6-nitro-L-arginine methylester (L-NAME) into the renal medullary interstitial space resulted in decreased interstitial fluid pressure and reduced sodium excretion. The mechanisms by which small elevations in renal interstitial fluid pressure alter tubular sodium reabsorption remain to be determined. PRESSURE-NATRIURESIS EFFECTS IN HYPERTENSIVE RATS: Our studies have also shown that the pressure-natriuresis response is blunted in spontaneously hypertensive rats (SHR) compared to normotensive Wistar-Kyoto (WKY) rats. This abnormality is associated with shifts in the relationships among papillary flow, renal interstitial pressure and renal perfusion pressure towards higher pressures. The calcium antagonist nisoldipine corrected the defect in vasa recta hemodynamics in SHR and normalized relationships among sodium excretion, renal interstitial pressure and renal perfusion pressure. CONCLUSIONS: These studies indicate that sodium and water excretion is very sensitive to small changes in renal perfusion pressure due to associated changes in papillary blood flow, and that alterations in medullary hemodynamics can have an important effect on the relationship between arterial pressure and sodium and water excretion.

Animals↗

PubMed1992

Angiotensin II influences the renal hemodynamic response to blockade of thromboxane A2 and prostaglandin H2 receptors.

This study was designed to examine the influence of angiotensin II on the renal hemodynamic response to blockade of thromboxane A2 and prostaglandin H2 receptors with SQ29548 (2 mg/kg, i.v. bolus, plus 2 mg kg-1 hr-1 infusion) in anesthetized rats. In control rats without any pretreatment, SQ29548 did not change blood pressure, but increased renal blood flow from 7.0 +/- 0.4 to 7.7 +/- 0.4 ml min-1 g kidney weight-1 (P < .05) and decreased renal vascular resistance from 18.1 +/- 1.0 to 16.2 +/- 0.8 mm Hg/ml min-1 g kidney weight-1 (P < .05). In contrast, SQ29548 was without effect on renal blood flow or renal vascular resistance in rats pretreated with saralasin or captopril to block angiotensin II actions and formation, respectively. SQ29548 also increased renal blood flow and decreased renal vascular resistance in rats pretreated with captopril in which the plasma concentration of angiotensin II was fixed at elevated levels by concurrently infusing the peptide at doses ranging from 5 to 80 ng/min. In this experimental setting, the administration of SQ29548 reduced preglomerular vascular resistance selectively. Because, according to previous studies, SQ29548 does not interfere with the direct vasoconstrictor actions of angiotensin II, the renal vasodilatory effect of SQ29548 in rats with elevated plasma angiotensin II is attributable to interference with the operation of mechanisms of vasoconstriction mediated by activation of thromboxane A2-prostaglandin H2 receptors. We conclude that the status of the renin-angiotensin system is a determinant of the renal vasodilatory response to SQ29548.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1992

Effect of clentiazem on arterial pressure and renal function in normotensive and hypertensive rats.

The present study evaluated the effects of a new benzothiazepine calcium channel antagonist, clentiazem, on arterial pressure and renal function in spontaneously hypertensive rats (SHR), normotensive Wistar-Kyoto (WKY) and Munich-Wistar rats (MWR). Administration of clentiazem in doses from 1 to 20 micrograms/kg/min produced dose-dependent increases in sodium and water excretion in MWR, reaching maximum values of 292 and 376% of control, respectively, at the 20-micrograms/kg/min dose. Clentiazem (10 micrograms/kg/min) lowered arterial pressure by 16% and doubled glomerular filtration rate (GFR) in MWR. The rise in GFR was associated with an increase in glomerular capillary pressure of 16 mm Hg, produced by a combination of preglomerular vasodilation and efferent arteriolar vasoconstriction. In SHR, administration of clentiazem (10 micrograms/kg/min) lowered arterial pressure by 30 mm Hg and increased urine flow and sodium excretion by 137 and 200%, respectively. In WKY rats, the same dose of clentiazem decreased arterial pressure by only 10 mm Hg, whereas urine flow and sodium excretion increased 62 and 38%, respectively. A high dose of clentiazem (1 mg/kg bolus plus 1 mg/kg/hr infusion i.v.) lowered arterial pressure by 63 mm Hg in SHR. Renal vascular resistance fell by 39% and there was a 5-fold increase in sodium excretion. In WKY rats, the same dose of clentiazem reduced arterial pressure by 20 mm Hg, but it had no significant effect on sodium excretion. These results indicate that clentiazem increases sodium excretion and GFR in normotensive rats in part by preferentially dilating the renal preglomerular vasculature. This compound is also an antihypertensive agent that lowers arterial pressure and promotes sodium excretion in SHR.

Animals↗

PubMed1991

Pilon fractures of the proximal interphalangeal joint.

A pilon fracture is an uncommon intraarticular fracture of the proximal interphalangeal (PIP) joint resulting in comminution, central depression, and splay, sagittally and coronally, of the articular surface of the base of the middle phalanx. This study reviews three treatment methods and results in 20 patients. Injury was produced by an axial load and occurred primarily to the ulnar digits. Clinical and radiographic follow-up averaged 25 months. Treatment was divided into three categories: splint (four patients), skeletal traction through the middle phalanx (seven patients), and open reduction with Kirschner pins (nine patients). Anatomic restoration of PIP articular contour was not achieved, regardless of technique. No patient regained full mobility at either interphalangeal joint. Treatment by immobilization is undesirable. Open reduction should be approached cautiously and may result in significant complications. Skeletal traction is safe and gives results that are radiographically and clinically comparable to those achieved with open reduction.

Adult↗

PubMed1991

Pathways linking renal excretion and arterial pressure with vascular structure and function.

1. A brief review is presented which summarizes the role of the kidney in the long-term regulation of arterial pressure and the mechanism whereby changes in body fluid volume can influence the function and structure of the systemic vasculature. 2. Studies indicate that the kidney detects changes of arterial pressure via changes of medullary blood flow which in the volume expanded state is poorly autoregulated. Elevations of renal arterial pressure raise vasa recta capillary pressure and renal interstitial fluid pressure, which in turn reduces tubular reabsorption of sodium and water. 3. The sensitivity of the pressure-diuresis relationship is controlled by renal sympathetic nerve activity and a variety of hormone and autocrine systems. 4. Evidence is also reviewed which shows that small changes of blood volume (5%) resulting from reduced renal excretion can acutely and chronically result in 25% increases of total peripheral resistance and arterial pressure. 5. Short-term increases of vascular resistance are predicted by regional autoregulatory responses while long-term elevations of vascular resistance appear to result from the structural changes of large vessel hypertrophy and microvascular rarefaction within skeletal muscle.

Animals↗

PubMed1991

Effects of 12-HETE on isolated dog renal arcuate arteries.

12-Hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) is one of the major noncyclooxygenase eicosanoids formed in vascular tissue. The vasoactive effects of the cytochrome P-450 product, 12(R)-HETE and the lipoxygenase product, 12(S)-HETE, on isolated, perfused renal arcuate arteries of the dog were investigated using videomicroscopy. R and S refer to stereoconfiguration of the hydroxy group at the twelfth position of this fatty acid structure. Cumulative doses of 12(R)-HETE produced a concentration-dependent vasoconstriction (n = 9) with a threshold dose of 10(-9) M. At a concentration of 3 x 10(-7) M, 12(R)-HETE reduced vascular diameter by 63 +/- 8 microns (from 306 +/- 17 microns), which was 37 +/- 6% of the maximal vasoconstrictor response to norepinephrine (10(-6) M). The effects of 12(R)-HETE were not altered by indomethacin (10(-6) M, n = 8). The vasoconstrictor response was associated with depolarization of vascular smooth muscle from -47 +/- 1 (15 cells) to -32 +/- 1 mV (12 cells). 12(S)-HETE was also a vasoconstrictor (n = 6), but the threshold concentration for vasoconstriction was 10(-8) M. Small renal arteries obtained from ischemic-injured, but not normal, kidneys produced a metabolite when incubated with arachidonic acid, which coeluted with a 12-HETE standard using reverse-phase high-pressure liquid chromatography. The rate of synthesis of this 12-HETE-like metabolite by renal arteries obtained from ischemic-injured and normal kidneys averaged 1.2 +/- 0.4 (n = 9) and 0.1 +/- 0.1 (n = 7) pmol.h-1.mg tissue-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1991

Influence of angiotensin II on pressure natriuresis and renal hemodynamics in volume-expanded rats.

This study examined whether angiotensin II (ANG II) influences the pressure-natriuretic (PN) response by altering renal cortical or medullary hemodynamics. Studies were performed in Inactin-anesthetized rats that were acutely volume expanded to maintain plasma renin activity and ANG II levels in the physiological range. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of norepinephrine, vasopressin, cortisol, and aldosterone were fixed by intravenous infusion. In control rats (n = 8), sodium excretion increased from 3 to 17 microeq.min-1.g kidney wt-1 as renal perfusion pressure (RPP) was elevated from 96 to 141 mmHg (n = 8). Captopril (2 mg/kg, n = 9) reduced plasma levels of ANG II from 48 +/- 5 to 18 +/- 2 pg/ml, but it did not alter the PN relationship. Infusion of ANG II (20 ng.kg-1.min-1, n = 9) increased plasma levels of ANG II to 232 +/- 42 pg/ml and shifted the PN relationship to the right by 14 mmHg. Captopril increased renal blood flow, and infusion of ANG II returned it to control. Captopril had no effect on glomerular filtration rate (GFR) or glomerular capillary pressure (Pglom); however, subsequent ANG II infusion decreased Pglom from 56 +/- 2 to 48 +/- 2 mmHg and reduced GFR by 30%. Neither captopril nor ANG II altered papillary bloodflow or vasa recta capillary pressure at normal levels of RPP. These results indicate that the shift of the PN relationship during infusion of ANG II is due to a decrease in filtered load and enhanced tubular reabsorption of sodium. Acute blockade of the renin-angiotensin system had little effect on the PN response in volume-expanded rats despite affecting renal hemodynamics, because either the plasma and/or intrarenal levels of ANG II were already suppressed below those needed to influence tubular function or volume expansion inhibits tubular reabsorption in the nephron segments normally influenced by ANG II.

Aldosterone↗

PubMed1991

Pressure natriuresis and cortical and papillary blood flow in inbred Dahl rats.

The present study examined whether alterations in papillary blood flow, renal interstitial pressure (RIHP), and the pressure-natriuretic (PN) response are associated with the development of hypertension in inbred Dahl salt-sensitive (Dahl-S) rats. The PN responses were compared in 18- to 20-wk-old, Inactin-anesthetized, inbred Dahl salt-sensitive (S/Jr) and salt-resistant (R/Jr) rats fed a low-(0.3%) and a high- (8.0%) sodium chloride diet. Cortical and papillary blood flows were measured using laser-Doppler flowmetry. Neural and hormonal influences on the kidney were controlled by renal denervation and by fixing plasma norepinephrine, vasopressin, corticosterone, and aldosterone levels by intravenous infusion. The slope of the PN relationship in S/Jr rats maintained on a low-salt diet was 62% lower than that observed in R/Jr rats; however, whole kidney, cortical, and papillary blood flows and RIHP were not significantly different at any perfusion pressure studied. Glomerular filtration rate (GFR) was 25% lower in S/Jr rats than in R/Jr animals maintained on a low-salt diet. The slopes of the PN responses were similar in S/Jr and R/Jr rats exposed to a high-salt diet, but the entire relationship was shifted toward higher pressures by 20 mmHg in the S/Jr rats. Control cortical and papillary blood flows measured at control mean arterial pressures of 126 +/- 3 and 167 +/- 5 mmHg in R/Jr and S/Jr rats, respectively, were not significantly different. However, cortical and papillary blood flows were 25% lower in the S/Jr than in the R/Jr rats exposed to a high-salt diet when compared at equivalent renal perfusion pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Role of kinins and angiotensin II in the renal hemodynamic response to captopril.

This study examined the role of angiotensin II (ANG II), kinins, and prostaglandins in the renal hemodynamic response to captopril in Munich-Wistar rats in which plasma renin activity was elevated [18.8 +/- 3.3 ng angiotensin I (ANG I).ml-1.h-1]. Neural influences on the kidney were eliminated by renal denervation, and renal perfusion pressure (RPP) was controlled using a clamp on the aorta. Urine flow, sodium excretion, renal blood flow (RBF), glomerular filtration rate (GFR), and cortical and papillary red blood cell (RBC) flow increased significantly after captopril (2 mg/kg iv). Glomerular and peritubular capillary pressures rose by 20%, and vasa recta capillary pressure fell by 3-4 mmHg due to significant reductions in estimated preglomerular, efferent arteriolar and renal capillary-venous vascular resistances. Infusion of ANG II (20 ng.kg-1.min-1 iv) returned RBF, GFR, and glomerular and peritubular capillary pressures to control; however, ANG II did not lower papillary RBC flow before inhibition of prostaglandin synthesis. Saralasin had no effect on papillary RBC flow or the response to captopril. The changes in vasa recta hemodynamics produced by captopril were blocked by a kinin antagonist. These findings indicate that ANG II exerts a vasoconstrictor influence on the renal cortical vasculature of Munich-Wistar rats; however, its effects on the medullary circulation are opposed by vasodilatory eicosanoids. They also suggest that kinins participate in the papillary RBC flow response to captopril, perhaps by reducing the outflow resistance from the vasa recta circulation.

Angiotensin II↗

PubMed1991

Effect of volume expansion on papillary blood flow and sodium excretion.

The present study examined whether changes in plasma oncotic pressure or hematocrit play a role in the redistribution of renal blood flow and the natriuretic response to extracellular fluid volume (ECFV) expansion with saline. Intravenous infusion of saline produced a 46% increase in the flow of red blood cells (RBCs) in the papilla of Inactin-anesthetized euvolemic Munich-Wistar rats (n = 6). This was primarily due to an increase in the number of functional capillaries perfused with moving RBCs, as indicated both by laser-Doppler flowmetry and videomicroscopy. The velocity of RBCs in ascending or descending vasa recta was not significantly altered by the infusion of saline. Plasma volume expansion with a 6% solution of albumin (n = 6) did not increase papillary RBC flow, whereas volume expansion with whole blood produced a 17% increase in the flow of RBCs in the papilla. Sodium excretion after ECFV expansion with saline (n = 6) was greater than that seen after plasma volume expansion with a 6% solution of albumin (n = 5). The results indicate that the rise in papillary RBC flow after ECFV expansion with saline is due to an increase in the number of perfused vasa recta capillaries. The failure of plasma volume expansion to alter papillary RBC flow suggests that changes in plasma oncotic pressure and/or renal interstitial pressure may signal the rise in papillary RBC flow after intravenous infusion of saline. The present study also indicates that laser-Doppler flowmetry is a useful technique to monitor changes in the flow, velocity, and concentration of moving RBCs in tissue.

Albumins↗

PubMed1991

Enhanced chloride reabsorption in the loop of Henle in Dahl salt-sensitive rats.

This study examines the nephron segments contributing to the blunted pressure-natriuretic response in Dahl salt-sensitive rats. Urine and late proximal and early distal tubular fluid samples were collected from 16-20-week-old, inbred Dahl salt-sensitive (DS/Jr) and salt-resistant (DR/Jr) rats, and Dahl salt-sensitive (DS) and salt-resistant (DR) rats from the Brookhaven colony, that were maintained from birth on a low (0.3%) sodium chloride diet. Urine flow and sodium and chloride excretions were 65% less in the DS/Jr than in the DR/Jr rats when their kidneys were perfused at an equal renal perfusion pressure of approximately 150 mm Hg. The percentages of the filtered load of water and chloride remaining at the end of the proximal tubule were significantly greater in DS/Jr rats than in DR/Jr rats; however, the percentages of the filtered load of water and chloride reaching the early distal tubule were significantly less, by 29% and 77%, respectively. Fractional reabsorption of water and chloride in the loop of Henle of DS/Jr rats was twice that observed in DR/Jr rats. Similar results were obtained in DS and DR rats of the Brookhaven strain. Urine flow and sodium and chloride excretions were 60% lower in DS than in DR rats at a renal perfusion pressure of 135 mm Hg. Proximal tubular reabsorption of water and chloride was similar in DS and DR rats; however, the percentages of the filtered load of water and chloride reabsorbed in the loop of Henle were greater in DS than in DR rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1991

Effect of an angiotensin II and a kinin receptor antagonist on the renal hemodynamic response to captopril.

The role of angiotensin II and kinins on the renal cortical and papillary hemodynamic and on the sodium and water excretory responses to converting enzyme inhibition with captopril was examined in euvolemic Munich-Wistar rats. Cortical and papillary blood flows were measured using a laser Doppler flowmeter. Cortical blood flow increased 28% after blockade of angiotensin II receptors with DuP 753 (2 mg/kg i.v., n = 6). Captopril (2 mg/kg i.v., n = 6) had no effect on cortical blood flow in rats pretreated with the angiotensin II antagonist. DuP 753 had no effect on papillary blood flow, nor did it prevent the rise in papillary blood flow produced by captopril (2 mg/kg, n = 6). Infusion of a kinin receptor antagonist, D-Arg, [Hyp3,Thi5,8,D-Phe7]-bradykinin (2.5 micrograms/min i.v.), reduced basal papillary blood flow by 15% and blocked the rise in papillary blood flow produced by captopril. Renal blood flow rose by 11% after DuP 753 (2 mg/kg, n = 6), and subsequent administration of captopril and the kinin antagonist had no effect on renal blood flow. Urine flow and sodium excretion increased after DuP 753, but captopril produced additional increases in urine flow and sodium excretion of 68% and 46% respectively. Fractional sodium excretion rose from 0.85 +/- 0.15% to 1.56 +/- 0.14% after captopril. Infusion of the kinin antagonist returned sodium and water excretion to control levels, but fractional sodium excretion was not significantly altered. Glomerular filtration rate was not altered by DuP 753 or captopril; however, it fell from 1.6 +/- 0.1 to 1.2 +/- 0.1 ml/min/g kidney wt during infusion of the kinin antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMed1991

Inhibitors of cytochrome P-450 attenuate the myogenic response of dog renal arcuate arteries.

The role of cytochrome P-450 in the myogenic response of isolated, perfused renal arcuate arteries of dogs to elevations in transmural pressure was examined. The phospholipase A2 inhibitor oleyloxyethylphosphorylcholine (1 and 10 microM) inhibited the greater than threefold increase in active wall tension in these arteries after an elevation in perfusion pressure from 80 to 160 mm Hg. Inhibition of cyclooxygenase activity with indomethacin (1 or 10 microM) had no effect on this response. The cytochrome P-450 inhibitors ketoconazole (10 and 100 microM) and beta-diethyl-aminoethyldiphenylpropylacetate (SKF 525A, 10 and 100 microM) also inhibited the myogenic response. At a pressure of 160 mm Hg, SKF 525A (10 microM) and ketoconazole (100 microM) reduced active wall tension in renal arteries by approximately 70%. Partial inhibition of the myogenic response was obtained after perfusion of the vessels with mechanism-based inhibitors of P-450, 1-aminobenzotriazole (75 microM) and 12-hydroxy-16-heptadecynoic acid (20 microM). The thromboxane receptor antagonist SQ 29,548 (1 or 10 microM) had no effect on the pressure-induced increase in active wall tension in renal arteries. Arachidonic acid (50 microM) constricted isolated perfused renal arteries and potentiated the myogenic response in the presence of indomethacin. This response was completely reversed by ketoconazole (100 microM) or SKF 525A (100 microM). Microsomes (1 mg/ml) prepared from small renal arteries (200-500 microns) and incubated with [1-14C]arachidonic acid (0.5 mu Ci, 50 microM) produced a metabolite that coeluted with 20-hydroxyeicosatetraenoic acid (20-HETE) during reversed-phase high-performance liquid chromatography. The formation of this product was inhibited by both ketoconazole and SKF 525A at concentrations of 10 and 100 microM. These results are consistent with the involvement of the vasoconstrictor 20-HETE and other cytochrome P-450 metabolites of endogenous fatty acids in the myogenic response.

Animals↗

PubMed1991

Mesangial cell immune injury: effects of thromboxane receptor antagonism.

We assessed the renal hemodynamic changes occurring acutely after glomerular mesangial cell immune injury and the effects of thromboxane receptor antagonism on these changes. A single intravenous proteinuric dose of a monoclonal antibody raised against the rat thymocyte antigen Thy 1.1 (ER4), which is also expressed in rat mesangial cells, induced acute decrements in glomerular filtration rate and in renal blood flow in male Munich-Wistar rats. One hour after administration of 4 to 6 mg/kg of ER4 antibody, glomerular filtration rate and renal blood flow decreased by 80 and 36%, respectively. These decrements were associated with significant increments in basal thromboxane B2 synthesis in isolated glomeruli and no changes in glomerular prostaglandin E2 synthesis. Pretreatment of animals with the thromboxane receptor antagonist SQ-29,548 (2 mg/kg) significantly ameliorated decrements in glomerular filtration rate and renal blood flow. Pretreatment with a structurally dissimilar thromboxane receptor antagonist, L-670,596 (3 mg/kg) had no effect. Both antagonists at the doses employed abolished the decrements in renal blood flow induced by systemic administration of the thromboxane mimetic U-46619. Whereas the SQ-29,548 antagonist had no effect on glomerular leukotriene B4 and 12-hydroxyeicosatetraenoic acid synthesis, the L-670,596 thromboxane receptor antagonist significantly inhibited glomerular synthesis of these eicosanoids in immunologically injured glomeruli. These observations indicate that in mesangial cell immune injury the protective effect of thromboxane A2 receptor antagonism on glomerular filtration rate and renal blood flow is not solely due to inhibition of the vasoconstrictor effects of thromboxane A2. An effect on the synthesis of arachidonate lipoxygenation products may also play a role.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1991

Direct studies on the control of the renal microcirculation.

Recent advances in videomicroscopy combined with the development of several innovative in vivo and in vitro preparations now allow for direct study of the renal microcirculation. Blood flow in vasa recta capillaries of the rat can be studied by using video-microscopy, and changes in the flow of red blood cells in the renal cortex and papilla can be continuously monitored by using laser-Doppler flowmetry. All elements of the renal microcirculation can be visualized with the in vitro perfused juxtamedullary nephron or hydronephrotic kidney preparations. Pressures, blood flows, and vascular diameters in individual vessels can be directly measured in these preparations. Renal arterioles can be microdissected from the kidneys of several species and cannulated and pressurized in vitro for the study of pressure-diameter relationships and vascular responses to different agonists. In addition, membrane potentials and intracellular ion concentrations can now be measured in isolated renal arterioles by using microelectrodes and fluorescence microscopy. Thus, it is possible to study the control of renal vascular tone at all levels of integration from signal transduction in isolated cells to direct analysis of the regulation of hemodynamics in different regions of the microcirculation of the kidney in intact animals.

Animals↗

PubMed1990

Alterations in renal medullary hemodynamics and the pressure-natriuretic response in genetic hypertension.

The concept that the kidney plays a major role in the long-term control of arterial pressure is based on the pressure-natriuretic response. According to this hypothesis, hypertension can only develop when the relationship between sodium excretion and arterial pressure is altered. Transplantation studies have indicated that some form of renal dysfunction underlies the development of genetic forms of hypertension in the spontaneously hypertensive rat (SHR) and in the Dahl salt-sensitive (S) rat. Nonetheless, the factors responsible for "resetting the kidney in hypertension" remain unknown. We have reported that the pressure-natriuretic relationships of SHR and Dahl S rats of the Brookhaven and Rapp strains are shifted toward higher pressures prior to the development of the disease. Papillary blood flow is also reduced in very young "prehypertensive" SHR. Recent studies on the mechanism of pressure-diuresis indicate that it is mediated by inhibition of sodium reabsorption in the proximal tubule and/or thin descending limb of Henle of deep nephrons. It is also associated with changes in renal interstitial pressure and the pressure and flow in the vasa recta circulation. These observations suggest that an elevation in renal medullary vascular resistance may be responsible for shifting the pressure-natriuresis relationship toward higher pressures in hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗