The evolution of early fibromuscular lesions hemodynamically induced in the dog renal artery. I. Light and transmission electron microscopy.
In view of the important roles of arterial intimal fibromuscular lesions as precursors of atherosclerotic plaque and occlusive lesions in arterial reconstructions, a model has been developed for the rapid hemodynamic induction of these lesions by anastomosis of the dog right renal artery to the inferior vena cava. Light and transmission electron microscopic observations were made on the arterial shunt after periods of rapid flow ranging form 10 minutes to 2 hours to identify initial factor(s) and evolutionary mechanisms in the etiology of the lesions. The sequence of events included aberrations in ruthenium red staining of the endothelial luminal membrane at 10 minutes, multilayered thickening of the subendothelial basement membrane (BM) at 15 minutes, and initial reorientation and migration of smooth muscle cells (SMC) into the intima along with the appearance of areas of degeneration of the internal elastic lamina (IEL) at 30 minutes. The endothelial cells were still intact in some areas overlying the SMC migration and IEL degeneration, but they were separating from the surface in other such areas. As subendothelium became exposed, some platelet adherence was noted. By 2 hours, the entire wall reaction was fully developed. Initial observations indicate that in the evolution of this hemodynamically induced lesion visible alteration in the endothelial cells is not prerequisite to degeneration of the underlying IEL and reorientation and migration of medial SMC. (+info)
Prevalence of angiographic atherosclerotic renal artery disease and its relationship to the anatomical extent of peripheral vascular atherosclerosis.
BACKGROUND: Recognition of the possible presence of atherosclerotic renal artery disease (ARAD) is important because of its progressive nature, and because of the potential for precipitating an acute deterioration in renal function by administration of angiotensin-converting enzyme inhibitors. The aim of this study was to identify the prevalence of ARAD in patients undergoing peripheral angiography and its relationship to the extent of their peripheral vascular disease (PVD). METHODS: The reports of the 218 patients who underwent peripheral angiography to investigate PVD in one centre in a calendar year, and in whom it was possible to image the renal arteries, were analysed retrospectively. The presence of atherosclerotic disease in the renal, aortic, iliac, femoral and distal areas was recorded for each patient. RESULTS: The prevalence of ARAD was 79/218 (36.2%). The greater the number of atherosclerotic areas of the arterial tree, the higher the prevalence of ARAD. Patients with aortic disease and bilateral iliac, femoral and distal vessel disease had the highest incidence of ARAD 19/38 (50%). The incidence of ARAD in those with femoral artery atherosclerosis was significantly higher than in those without femoral artery atherosclerosis (42.1% compared with 9.7%, P=0.001 chi2). There was no significant difference in those groups with or without iliac and distal disease. None of the 11 patients with normal femoral and iliac arteries had ARAD. CONCLUSIONS: Renal artery atherosclerosis is a common occurrence in patients with PVD. If extensive PVD is recognized during aortography, a high flush should be considered to examine the renal arteries, if they are not included in the main study. (+info)
NH2-terminal fragments of the 130 kDa subunit of myosin phosphatase increase the Ca2+ sensitivity of porcine renal artery.
1. The effects of the NH2-terminal fragments of M130, a 130 kDa regulatory subunit of smooth muscle myosin phosphatase, on contraction and myosin light chain phosphorylation were investigated in Triton X-100-permeabilized porcine renal artery. 2. Incubation of the permeabilized fibres with M1301-633 (a fragment containing amino acid residues 1-633) or M13044-633 enhanced the Ca2+-induced contraction and shifted the [Ca2+]i-force relationship to the left (EC50 of Ca2+: 330 nM, control, without fragment; 145 nM, M1301-633; 163 nM, M13044-633). Pre-incubation for 1-3 h was needed for these long constructs. 3. M1301-374, M130304-511 and M130297-374, i.e. relatively short constructs compared with M1301-633 and M13044-633, also induced leftward shifts of the [Ca2+]i-force relationship (EC50 of Ca2+: 65 nM, 72 nM and 180 nM, respectively). However, these required no pre-incubation. 4. Deletion of residues 304-374 from the most potent construct, M1301-374, abolished the Ca2+-sensitizing effect. 5. Wortmannin inhibited the enhancement of contraction induced by M130 fragments when added before contraction was initiated and partially inhibited the effects when added after steady-state contraction. 6. M1301-374 slowed the rate of relaxation in Ca2+-free medium. The time for 50 % relaxation with this fragment was 510 +/- 51 s, compared with 274 +/- 14 s for control. 7. The levels of myosin light chain phosphorylation (22.4 %) and force (34. 5 %) obtained with 300 nM Ca2+ were increased by 3 microM M1301-374 to 35.7 and 92.2 %, respectively. However, M1301-374 had no effect on the phosphorylation-force relationship. 8. In conclusion, the NH2-terminal M130 fragments containing residues 304-374 inhibited myosin phosphatase, increased myosin light chain phosphorylation and increased the Ca2+ sensitivity of the contractile apparatus in permeabilized porcine renal artery. (+info)
Altered renal hemodynamics and impaired myogenic responses in the fawn-hooded rat.
The present study examined whether an abnormality in the myogenic response of renal arterioles that impairs autoregulation of renal blood flow (RBF) and glomerular capillary pressure (PGC) contributes to the development of renal damage in fawn-hooded hypertensive (FHH) rats. Autoregulation of whole kidney, cortical, and medullary blood flow and PGC were compared in young (12 wk old) FHH and fawn-hooded low blood pressure (FHL) rats in volume-replete and volume-expanded conditions. Baseline RBF, cortical and medullary blood flow, and PGC were significantly greater in FHH than in FHL rats. Autoregulation of renal and cortical blood flow was significantly impaired in FHH rats compared with results obtained in FHL rats. Myogenically mediated autoregulation of PGC was significantly greater in FHL than in FHH rats. PGC rose from 46 +/- 1 to 71 +/- 2 mmHg in response to an increase in renal perfusion pressure from 100 to 150 mmHg in FHH rats, whereas it only increased from 39 +/- 2 to 53 +/- 1 mmHg in FHL rats. Isolated perfused renal interlobular arteries from FHL rats constricted by 10% in response to elevations in transmural pressure from 70 to 120 mmHg. In contrast, the diameter of vessels from FHH rats increased by 15%. These results indicate that the myogenic response of small renal arteries is altered in FHH rats, and this contributes to an impaired autoregulation of renal blood flow and elevations in PGC in this strain. (+info)
Cyclosporine-induced renal artery smooth muscle contraction is associated with increases in the phosphorylation of specific contractile regulatory proteins.
Cyclosporine A (CSA) is a type 2B phosphatase inhibitor which can induce contraction of renal artery smooth muscle. In this investigation, we examined the phosphorylation events associated with CSA-induced contraction of bovine renal artery smooth muscle. Contractile responses were determined in a muscle bath and the corresponding phosphorylation events were determined with whole cell phosphorylation and two-dimensional gel electrophoresis. CSA-induced contractions were associated with increases in the phosphorylation of the 20 kDa myosin light chains (MLC20) and different isoforms of the small heat shock protein, HSP27. Cyclic nucleotide-dependent relaxation of CSA-induced contractions was associated with increases in the phosphorylation of another small heat shock protein, HSP20, and decreases in the phosphorylation of the MLC20, and some isoforms of HSP27. These data suggest that CSA-induced contraction and relaxation of vascular smooth muscle is associated with increases in the phosphorylation of specific contractile regulatory proteins. (+info)
Hypotensive response to captopril: a potential pitfall of scintigraphic assessment for renal artery stenosis.
A characteristic pattern seen on captopril renography is described that is due to systemic hypotensive response. Most patients with these findings on captopril renography do not receive renal artery angiograms in our clinic because it is usually recognized. However, this pattern has received little attention in the medical literature and may be misinterpreted as being due to physiologically significant renal artery hypertension. METHODS: Over the last 3 y, renal artery angiograms were performed on three patients with systemic hypotensive response pattern on captopril renography. This allowed a unique opportunity to correlate the results of the captopril renogram with the renal artery angiograms in this patient population. Captopril renography was performed with a glomerular filtration agent, diethylenetriamine pentaacetic acid (DTPA), and a tubular agent, o-iodohipurate (OIH). RESULTS: Renal artery angiograms showed no evidence of renal artery stenosis in three patients with systemic hypotensive response pattern on captopril renography. Systemic hypotension on captopril renograms results in preserved uptake of both DTPA and OIH and hyperconcentration in the cortex and collecting system. CONCLUSION: The systemic hypotensive response pattern seen on captopril renography is a distinctive pattern that does not represent physiologically significant renal artery stenosis. (+info)
The effects of crossing porcine renal artery ostia with various endovascular stents.
OBJECTIVES: To compare the effects of crossing renal artery ostia with various stents. METHODS: The renal artery ostia of 24 large white pigs were covered with a Wallstent (nine ostia), a Palmaz stent (nine ostia) and a Memotherm stent (13 ostia). After an interval of 6-15 weeks, aortography, renal pressure and blood samples were performed and the pigs then sacrificed for histological examination. RESULTS: Histological examination revealed an organised collagen matrix with endothelial cells covering the struts in contact with the aorta. This occurred with all stents but was most organised with the Wallstent. This matrix did not involve the renal artery ostia crossed by Wallstents, but in one Palmaz stent and in 12/13 Memotherm stents, a disorganised acellular matrix caused partial ostial occlusion. There was no mean fall in renal artery pressure but traces were damped in 8/13 cases of partial occlusion. There was a rise in serum creatinine in two cases using the Palmaz stent. CONCLUSIONS: Covering renal arteries with the Wallstent appears to be safe in the short-term. Placement of stents with larger struts across renal arteries will require imaging methods, such as intravascular ultrasound (IVUS) to ensure that the ostia are not obstructed. (+info)
Inhibition of prostaglandin and nitric oxide synthesis prevents cortisol-induced renal vasodilatation in sheep.
Glucocorticoids increase renal blood flow (RBF) and glomerular filtration rate in many species, but the mechanisms involved are unclear. We investigated whether cortisol-induced renal vasodilatation in conscious sheep depends on interactions with prostaglandins or angiotensin II. Intravenous infusion of cortisol (5 mg/h) for 5 h increased renal conductance (RC) by 1.06 +/- 0.24 ml. min-1. mmHg-1 more than vehicle. During intrarenal infusion of indomethacin (0.25 mg. kg-1. h-1), the cortisol-induced increase in RC (0.28 +/- 0.21 ml. min-1. mmHg-1) was significantly reduced. The cortisol-induced rise in RBF (103 +/- 17 ml/min) was not significantly reduced by indomethacin treatment (76 +/- 9 ml/min). Combined intrarenal infusion of indomethacin (0.25 mg. kg-1. h-1) with Nomega-nitro-L-arginine (2.0 mg. kg-1. h-1), a nitric oxide synthase inhibitor, abolished the cortisol-induced increases in both RC and RBF. Inhibition of angiotensin II synthesis with intravenous captopril (40 mg/h) blocked the renal vasoconstrictor action of angiotensin I but did not inhibit the cortisol-induced increases in RBF and RC. This study provides evidence that nitric oxide and prostaglandins play a role in cortisol-induced renal vasodilatation but indicates that this response is independent of an interaction with angiotensin. (+info)