Rabbit Renal Artery Research Articles

Levamisole Impairs Vascular Function by Blocking α-Adrenergic Receptors and Reducing NO Bioavailability in Rabbit Renal Artery

Levamisole is an anthelmintic drug restricted to veterinary use but is currently detected as the most widely used cocaine cutting agent in European countries. Levamisole-adulterated cocaine has been linked to acute kidney injury, marked by a decrease in glomerular filtration rate, which involves reduced renal blood flow, but data on the alteration of renovascular response produced by levamisole are scarce. Renal arteries were isolated from healthy rabbits and used for isometric tension recording in organ baths and protein analysis. We provide evidence that depending on its concentration, levamisole modulates renovascular tone by acting as a non-selective α-adrenergic receptor blocker and down-regulates α1-adrenoceptor expression. Furthermore, levamisole impairs the endothelium-dependent relaxation induced by acetylcholine without modifying endothelial nitric oxide synthase (eNOS) expression. However, exposure to superoxide dismutase (SOD) partially prevents the impairment of ACh-induced relaxation by levamisole. This response is consistent with a down-regulation of SOD1 and an up-regulation of NADPH oxidase 4 (Nox4), suggesting that endothelial NO loss is due to increased local oxidative stress. Our findings demonstrate that levamisole can interfere with renal blood flow and the coordinated response to a vasodilator stimulus, which could worsen the deleterious consequences of cocaine use.Graphical EFS electric field stimulation, NA noradrenaline, AR adrenergic receptor, IP3 inositol 1, 4, 5-trisphosphate, cAMP cyclic adenosine monophosphate, mAChR muscarinic acetylcholine receptor, eNOS endothelial nitric oxide synthase, sGC soluble guanylyl cyclase, SOD superoxide dismutase, NOX4 NAPH oxidase 4

Blocked-flow vs. free-flow cyanoacrylate glue embolization: Histological differences in an in vivo rabbit renal artery model

PurposeThe purpose of this in vivo animal study was to compare the acute histological effects on the arterial vessel wall of free-flow vs. blocked-flow embolization with metacryloxysulfolane-n‑butyl cyanoacrylate (MS-NBCA) in several concentrations. Materials and methodsA total of 42 rabbit renal arteries were embolized using MS-NBCA mixed with ethiodized oil. The MS-NBCA concentration was 12.5%, 25%, or 50%. All mixtures were injected under both free-flow and blocked-flow conditions. The rabbits were euthanised 30 min after arterial embolization. Arterial-lumen distension, intimal inflammation and necrosis, peri‑arterial edema, and distality of MS-NBCA penetration were assessed histologically. Multivariable regression analyses were performed using a manual backward procedure, with linear, ordinal and logistic regression to search for factors associated with these outcomes ResultsMarked or severe dilatation was observed in 36 out of 42 arteries (86%) and marked or transmural intimal arteritis in all 42 arteries (42/42; 100%). Lumen dilatation caused focal vessel-wall flattening, which resulted in intimal necrosis. Multifocal necrosis extending from the intima to the media occurred in 23 out of 42 kidneys (55%) and peri‑arterial edema with multifocal vascular leakage in 19 out of 42 kidneys (45%). At multivariable analysis, blocked-flow MS-NBCA injection was associated with greater severity of vessel-wall lesions, including intimal arteritis (P = 0.003) and intimal necrosis (P = 0.014), compared to free-flow injection. Blocked-flow injection was also associated with peri‑arterial edema (P = 0.008) and greater distality of MS-NBCA penetration (P = 0.001). ConclusionBlocked-flow MS-NBCA injection during renal artery embolization is significantly associated with more acute arterial-wall damage and greater distality of glue penetration compared to free-flow injection in a rabbit model. These preliminary findings may have clinical implications, as blocked-flow injection is routinely used to treat specific vascular diseases or malformations in human.

Cascade Reaction of "Mn2+ -Catechol" Triggered by H2 O2 to Integrate Firm Tumor Vessel Embolization and Hypoxic Response Relief.

Transcatheter arterial embolization (TAE) therapy requires firm and long-term vessel embolization without recanalization. However, firm embolization usually leads to unanticipated hypoxic response which promotes tumor recurrence and metastasis. Herein, an injectable thermosensitive hydrogel containing catechol groups and Mn2+ (PNDM) has been developed to enhance embolization and inhibit hypoxic response utilizing augmented H2 O2 after TAE. This novel embolic agent converts H2 O2 into hydroxyl radicals via Mn2+ -dependent Fenton-like reaction, which are subsequently scavenged through a "catechol-quinone" transition to suppress hypoxic responses. Quinone structure can not only make hydrogel internal structure more compact, but also enhance hydrogel adhesion to vessel wall. In vivo experiments confirm that the rabbit renal artery can be firmly embolized for 84 days. Studies in liver VX2 tumor-bearing rabbits demonstrate that the PNDM-based TAE can promote tumor necrosis, inhibit angiogenesis and tumor metastasis, and greatly prolong rabbit survival. This strategy opens new sights in the TAE therapy for liver cancer.

Effects of temperature alteration on viscosity, polymerization, and in-vivo arterial distribution of N-butyl cyanoacrylate-iodized oil mixtures

PurposeTemperature alteration can modify the polymerization of n-butyl cyanoacrylate (NBCA)-iodized oil mixtures during vascular embolization; its effects on viscosity, polymerization time, and intra-arterial distribution of the NBCA-iodized oil mixture were investigated.Materials and methodsIn vitro, the viscosities of NBCA, iodized oil, and NBCA-iodized oil mixtures (ratio, 1:1–8) were measured at 4–60 ºC using a rotational rheometer. The polymerization times (from contact with blood plasma to stasis) were recorded at 0–60 ºC using a high-speed video camera. In vivo, the 1:2 mixture was injected into rabbit renal arteries at 0, 20, and 60 ºC; intra-arterial distribution of the mixture was pathologically evaluated.ResultsThe mixtures’ viscosities decreased as temperature increased; those at 60 ºC were almost four to five times lower than those at 4 ºC. The polymerization time of NBCA and the 1:1–4 mixtures increased as temperature decreased in the 0–30 ºC range; the degree of time prolongation increased as the percentage of iodized oil decreased. The 0 ºC group demonstrated distributions of the mixture within more peripheral arterial branches than the 20 and 60 ºC groups.ConclusionWarming reduces the mixture’s viscosity; cooling prolongs polymerization. Both can be potential factors to improve the handling of NBCA-iodized oil mixtures for lesions requiring peripheral delivery.Secondary abstractTemperature alteration influences the polymerization time, viscosity, and intra-arterial distribution of NBCA-iodized oil mixtures. Warming reduces the viscosity of the mixture, while cooling prolongs polymerization.

Assessment of the embolization effect of temperature-sensitive p(N-isopropylacrylamide-co-butyl methylacrylate) nanogels in the rabbit renal artery by CT perfusion and confirmed by macroscopic examination

Transcatheter embolization is an important treatment method in clinical therapy, and vascular embolization material plays a key role in embolization. The temperature-sensitive p(N-isopropylacrylamide-co-butyl methylacrylate) (PIB) nanogel is a novel embolic agent. To evaluate the feasibility of the nanogel as a blood vessel embolization agent, we aimed to assess the effect of embolization with PIB nanogels in the rabbit renal artery by non-invasive computed tomography (CT) perfusion, macroscopic and histological examination. Ten healthy adult Japanese rabbits were used to implement RAE of PIB nanogels in their right kidneys. CT perfusion scans were performed pre- and post-treatment at various time-points (1, 4, 8, and 12 weeks). Two rabbits were euthanized and histologically examined at each time-point, and the remaining rabbits were euthanized at 12 weeks after embolization. The RAE efficacy of the nanogels was further confirmed by macroscopic and histological examination. The renal volume and renal blood flow (BF) of the right kidney were significantly decreased post-treatment compared with those pre-treatment (volume: pre, 9278 ± 1736 mm3; post 1 week, 5155 ± 979 mm3, P < 0.0001; post 4 weeks, 3952 ± 846 mm3, P < 0.0001; post 8 weeks, 3226 ± 556 mm3, P < 0.0001; post 12 weeks, 2064 ± 507 mm3, P < 0.0001. BF: pre, 530.81 ± 51.50 ml/min/100 ml; post 1 week, 0 ml/min/100 ml, P < 0.0001; post 4 weeks, 0 ml/min/100 ml, P < 0.0001; post 8 weeks, 0 ml/min/100 ml, P < 0.0001; post 12 weeks, 0 ml/min/100 ml, P < 0.0001). No revascularization or collateral circulation was observed on histological examination during this period, and PIB nanogels were dispersed in all levels of the renal arteries. Twelve weeks after embolization, CT perfusion showed no BF in the right renal artery and renal tissue, a finding that was consistent with histological examination showing complete embolization of the right renal artery with a lack of formation of collateral vessels. The effect of embolization on PIB was adequate, with good dispersion and permanency, and could be evaluated by non-invasive and quantitative CT perfusion.

Newly Developed N-butyl Cyanoacrylate (EG glue) for Arterial Embolization: A Preclinical Study in Rabbit Renal Artery

N-Butyl cyanoacrylate (NBCA) glue has been widely utilized for the endovascular management of various vascular pathologies ranging from acute visceral hemorrhage to arteriovenous malformations. Here, we investigate the effectiveness and safety of the newly developed NBCA glue (i.e., EG glue) compared to conventional glue (Histoacryl) for transcatheter arterial embolization (TAE) in rabbit renal arteries. Compared to Histoacryl, EG glue had similar physical properties and embolic efficacy. In both groups, necrotizing lesions in the vessel walls were observed in all rabbits, without significant differences. Based on these results, we believe that EG glue could be a promising alternate embolic material for treating various diseases.

Handling and performance characteristics of a new small caliber radiopaque embolic microsphere.

The in vitro and in vivo handling and performance characteristics of a small caliber radiopaque embolic microsphere, 40–90 μm DC Bead LUMI™ (LUMI40‐90), were studied. Microsphere drug loading and elution and effects on size, suspension, and microcatheter delivery were evaluated using established in vitro methodologies. In vivo evaluations of vascular penetration (rabbit renal artery embolization), long‐term biocompatibility and X‐ray imaging properties, pharmacokinetics and local tissue effects of both doxorubicin (Dox) and irinotecan (Iri) loaded microspheres (swine hepatic artery embolization) were conducted. Compared to 70–150 μm DC Bead LUMI (LUMI70‐150), LUMI40‐90 averaged 70 μm versus 100 μm, which was unchanged upon drug loading. Handling, suspension, and microsphere delivery studies were successfully performed. Dox loading was faster (20 min) and Iri equivalent (<10 min) while drug elution rates were similar. Contrast suspension times were longer with no delivery complications. Vascular penetration was statistically greater (rabbit) with no unexpected adverse safety findings (swine). Microspheres ± drug were visible under X‐ray imaging (CT) at 90 days. Peak plasma drug levels and area under the curve were greater for LUMI40‐90 compared to LUMI70‐150 but comparable to 70–150 μm DC BeadM1™ (DC70‐150). Local tissue effects showed extensive hepatic necrosis for Dox, whereas Iri displayed lower toxicity with more pronounced lobar fibrosis. LUMI40‐90 remains suspended for longer and have greater vessel penetration compared to the other DC Bead LUMI sizes and are similarly highly biocompatible with long‐term visibility under X‐ray imaging. Drug loading is equivalent or faster with pharmacokinetics similar to DC70‐150 for both Dox and Iri.

Experimental study on embolization of rabbit renal artery with gelatin sponge microspheres.

The objective of this study was to evaluate the degradation characteristics and embolic effect of gelatin microspheres (GMSs) produced domestically in China through an experimental study comparing the embolization of rabbit renal arteries using GMSs and tris-acryl microspheres. Sixteen healthy adult New Zealand white rabbits were randomly divided into two groups. Group A was embolized with GMSs produced in China with a diameter of 150-200 μm (n = 8), and Group B was embolized with tris-acryl microspheres with a diameter of 100-200 μm (n = 8). The renal arteries were embolized through femoral artery puncture and catheterization. Renal artery angiography rechecks and hematoxylin and eosin staining of tissue sections were performed at 1 day, 4 days, 7 days, and 14 days after embolization, respectively, to observe vascular recanalization, degradation of microspheres, and embolic effect. Group A: Digital subtraction angiography showed complete recanalization at 14 days. The changes in embolic necrotic areas at different time points after embolization were similar in the two groups. At 4 days after embolization, changes in glomerular structure were observed in the kidney on the embolic side. At 7 days after embolization, atrophy, degeneration, and necrosis of the glomeruli, as well as degeneration and inflammatory cell infiltration of the renal tubules, were observed in the kidney on the embolic side. At 14 days after embolization, extensive atrophy and hyalinization of the glomeruli were observed, and local renal tissue showed patchy fibrosis with calcification of internal tissue. Hyperplasia of fibrillar connective tissue was observed in the renal interstitium. The GMSs produced domestically in China can be completely degraded after embolizing blood vessels for 14 days. The GMSs are similar to tris-acryl microspheres in arterial embolization effect and are safe and effective.

Diabetes modifies the role of prostanoids and potassium channels which regulate the hypereactivity of the rabbit renal artery to BNP.

Diabetic nephropathy is associated with increased risk of cardiovascular disease. B-type natriuretic peptide (BNP) plays an important role in cardiovascular pathophysiology and therapeutics. The aim of the present study was to investigate the influence of experimental diabetes on the mechanisms that regulate the relaxant response of the rabbit renal artery to BNP. Arterial relaxations to BNP were enhanced in diabetic rabbits. Indomethacin enhanced BNP-induced relaxation in control rabbits but showed no effect in diabetic rabbits. BNP-induced release of thromboxane A2 or prostacyclin was not different in both groups of animals. Iberiotoxin had no effect on relaxations to BNP in both groups of animals. Charybdotoxin displaced to the right the concentration-response curve to BNP in both group of animals, and inhibited BNP-induced relaxation only in diabetic rabbits. Glibenclamide did not modify the BNP-induced relaxations in control rabbits, but inhibited it in diabetic rabbits. These results suggest that diabetes induces hypereactivity of the rabbit renal artery to BNP by mechanisms that at least include (1) a reduced vasoconstrictor influence of arachidonic acid metabolites via cyclooxygenase 2, which is not related with changes in thromboxane A2 and prostacyclin release from the arterial wall and (2) a selectively increased modulatory activity of KATP and endothelial IKCa channels.

Effects of levamisole, a cocaine adulterant, on adrenergic response in the rabbit renal artery

Effects of levamisole, a cocaine adulterant, on adrenergic response in the rabbit renal artery

Water-Borne Endovascular Embolics Inspired by the Undersea Adhesive of Marine Sandcastle Worms.

Transcatheter embolization is used to treat vascular malformations and defects, to control bleeding, and to selectively block blood supply to tissues. Liquid embolics are used for small vessel embolization that require distal penetration. Current liquid embolic agents have serious drawbacks, mostly centered around poor handling characteristics and toxicity. In this work, a water-borne in situ setting liquid embolic agent is described that is based on electrostatically condensed, oppositely charged polyelectrolytes-complex coacervates. At high ionic strengths, the embolic coacervates are injectable fluids that can be delivered through long narrow microcatheters. At physiological ionic strength, the embolic coacervates transition into a nonflowing solid morphology. Transcatheter embolization of rabbit renal arteries demonstrated capillary level penetration, homogeneous occlusion, and 100% devascularization of the kidney, without the embolic crossing into venous circulation. The benign water-borne composition and setting mechanism avoids many of the problems of current liquid embolics, and provides precise temporal and spatial control during endovascular embolization.

The role of calcium entry on the relaxation response of rho-kinase inhibitor in rabbit renal artery

This study was performed to clarify the role of extracellular and intracellular Ca2+ on rho-kinase enzyme inhibition-induced relaxation in rabbit renal arteries. The response to rho-kinase inhibitor (Y-27632) was studied in isolated renal artery segments precontracted with phenylephrine in the presence of voltage-gated calcium channel blocker nifedipine and in the absence of intracellular or extracellular Ca2+. Cumulative addition of rho-kinase inhibitor Y-27632 (10-8-10-5 M) produced a concentration-dependent relaxation in renal artery rings precontracted with phenylephrine. Preincubation with nifedipine (1µM) resulted in a significant increase in relaxation response to rho-kinase inhibitor Y-27632 compared with preincubation with DMSO; the solvent of nifedipine. The maximal relaxation to Y-27632 in renal arteries precontracted with phenylephrine was significantly increased in the Ca-free Krebs containing 100 μmol/l ethylene glycol tetraacetic acid (EGTA) but after depletion of intracellular stores with 20 mmol/l caffeine and 1mmol/l EGTA in Ca2+ free Krebs there was no significant difference between the relaxation to Y-27632 from control response in 2.5 mmol/l Ca2+ Krebs in the renal artery. These results suggest the involvement of extracellular Ca and L-type voltage-operated Ca2+ channels in phenylephrine-induced rho-kinase activation (Fig. 3, Ref. 20).

Gelatin Microspheres: Correlation between Embolic Effect/Degradability and Cross-linkage/Particle Size

To evaluate the embolic effect and degradability of gelatin microspheres (GMS) using various degrees of cross-linkage and particle sizes in rabbit renal artery embolization. Four types of GMS were used, as follows: 2 types of cross-linkage and 2 types of particle size. Twenty-four rabbits (6 in each group) were used for the renal artery embolization. Renal angiography was performed before and after embolization of right renal artery. Follow-up renal angiography was performed 2 days (n=2), 5days (n=2), and 15 days (n=2) after embolization in each group, and then kidneys were removed for histopathological evaluation. Vascular areas of the angiography were measured by Image J software, and the reperfusion rate was calculated. In renal specimens, residual GMS were checked and the degree of degradation was classified according to a 4-point scale. The mean amounts of large- and small-particle-size GMS injected were 15.0 and 34.3mg, respectively. Tissue necrosis was confirmed in each group; however, no difference was observed among groups. Renal reperfusion was observed more with small GMS than with large GMS. Renal reperfusion was also observed more with low cross-linked GMS than with high cross-linked GMS. In histopathological specimens, large GMS were confirmed in lobar artery, and small GMS were confirmed in lobular artery. Low cross-linked GMS completely degraded 15 days after embolization. In contrast, high cross-linked GMS were persistent 15 days after embolization. Degree of cross-linkage and particle size affected degradability and reperfusion.

Diabetes impairs the atrial natriuretic peptide relaxant action mediated by potassium channels and prostacyclin in the rabbit renal artery

Diabetes is associated with increased prevalence of hypertension, cardiovascular and renal disease. Atrial natriuretic peptide (ANP) plays an important role in cardiovascular pathophysiology and is claimed to have cardioprotective and renoprotective effect in diabetic patients. The working hypothesis was that alloxan-induced diabetes might modify the vascular effects of ANP in isolated rabbit renal arteries and the mechanisms involved in such actions. Plasma ANP levels were higher in diabetic rabbits than in control rabbits. ANP (10−12–10−7M) induced a relaxation of precontracted renal arteries, which was lower in diabetic than in control rabbits. In arteries from both groups of animals, endothelium removal decreased the ANP-induced relaxation but inhibition of NO-synthesis did not modify ANP-induced relaxations. In KCl-depolarised arteries, relaxation to ANP was almost abolished both in control and diabetic rabbits. Tetraethylammonium (TEA) partly inhibited the relaxation to ANP in control rabbits but did not modify it in diabetic rabbits. Glibenclamide and 4-aminopyridine inhibited the relaxation to ANP, and these inhibitions were lower in diabetic than in control rabbits. Indomethacin potentiated the relaxation to ANP, more in control than in diabetic rabbits. In the presence of ANP the renal artery released thromboxane A2 and prostacyclin, and the release of prostacyclin resulted decreased in diabetic rabbits. The present results suggest that diabetes produces hyporeactivity of the rabbit renal artery to ANP by mechanisms that at least include the reduced modulation by prostacyclin and a lower participation of ATP-sensitive K+ channel (KATP), voltage-sensitive K+ channels (KV) and TEA-sensitive K+ channels (KCa).

Vasorelaxant mechanisms of ketamine in rabbit renal artery

BackgroundKetamine is a non-barbiturate anesthetic agent which has various effects on the cardiovascular system. Among them, ketamine is known for its hypotensive properties. The hypotension is thought to be mediated by a direct effect on vascular smooth muscles. This study is designed to examine the effects of ketamine on KCl- and histamine-induced contraction in isolated rabbit renal arteries.MethodsEndothelium-intact or -denuded smooth muscle rings were prepared and mounted in myographs for isometric tension measurements. The inhibitory effect of ketamine were investigated in smooth muscle rings precontracted with either 50 mM KCl- or 10 µM histamine.ResultsKetamine (0.1-100 µg/ml) produced similar concentration-dependent inhibition of contractile responses induced by either 50 mM KCl or 10 µM histamine. The respective IC50 values measured for ketamine following precontractions by 50 mM KCl and 10 µM histamine were 28.9 µg/ml (105.5 µM) and 26.7 µg/ml (97.5 µM). The inhibitory effect of 30 µg/ml ketamine were similarly observed after removal of endothelium or pretreatment with NG-Nitroarginine Methyl Ester (0.1 mM). The inhibitory effect of 30 µg/ml ketamine on histamine-evoked contraction was reduced by either tetraethylammonium (10 mM) or iberiotoxin, a large conductance Ca2+-activated K+ channel blocker. However, depletion of intracellular Ca2+ stores by ryanodine (10 µM) or thapsigargin (10 µM) showed no significant effect on 30 µg/ml ketamine-induced relaxation. Pre-incubation with 30 µg/ml ketamine significantly inhibited CaCl2-induced contraction at almost all ranges of concentration.ConclusionsKetamine-induced relaxation of rabbit renal arteries is mediated by both the activation of large conductance Ca2+-activated K+ channel and the inhibition of Ca2+ influx.

The morphology and haemodynamics of the rabbit renal artery: evaluation by conventional and contrast-enhanced ultrasonography

The purpose of this study was to test the morphology and haemodynamics of the renal artery in the rabbit as evaluated by conventional and contrast-enhanced ultrasonography (CEUS). The morphology and haemodynamics of the rabbit renal artery, including the diameter, which were measured using B-mode ultrasonography (US), colour Doppler US and CEUS, and systolic velocity, diastolic velocity and resistive index (RI) were measured using pulsed wave Doppler US. CEUS was used to measure the renal artery diameter: 0.21 ± 0.04 cm (right) and 0.21 ± 0.03 cm (left). Values of the main renal artery diameter obtained from CEUS significantly correlated with those of digital subtraction angiography. The blood flow velocity of the right main renal artery was 44.20 ± 8.71/18.92 ± 6.26 cm/s (systolic/diastolic) and 36.30 ± 6.89/17.64 ± 5.58 cm/s (systolic/diastolic), at its origin from the aorta and at the renal hilus, respectively. The blood flow velocity of the left main renal artery was 45.10 ± 8.49/19.00 ± 6.80 cm/s (systolic/diastolic) and 41.70 ± 10.25/19.55 ± 7.90 cm/s (systolic/diastolic), at its origin from the aorta and at the renal hilus, respectively. Conventional US provides a more feasible modality for measuring the morphology and haemodynamics of the rabbit renal artery. CEUS is a more accurate method for measuring diameter. This information on the morphology and haemodynamics of the rabbit renal artery might be helpful for researchers.

A Radiofrequency Electrode Catheter–Guide Wire System for Arterial Occlusion

Purpose To describe the design of a radiofrequency (RF) electrode catheter/guide wire system to allow endovascular coagulation of vessels. Materials and Methods A circuit was created by modifying an ordinary microcatheter. An electrically conductive ring was placed at a microcatheter tip, and an extension lead at the hub site. They were each connected to an inherent coil mesh. The rings (ie, cathodes) were 1, 3, 5, 10, and 20 mm in length. In egg white, a coagulation study was performed by changing the length of the guide wire (ie, anode; 1, 3, 5, 10, 20, and 40 mm) in each cathode at 20 W. The coagulation time and site were analyzed. In rabbits, the renal artery was ablated with the use of a 20-mm cathode and 10-mm anode. Results In the egg white study, the coagulation time was proportionally increased and was dependent on the lengths of the cathode and anode ( P < .05). Coagula developed at the anode to the 3-mm protrusion for the 1-mm cathode, to the 5-mm protrusion for the 3-mm cathode, to the 5-mm protrusion for the 5-mm cathode, to the 10-mm protrusion for the 10-mm cathode, and to the 20-mm protrusion for the 20-mm cathode. In rabbits, the renal artery was successfully occluded. Pathologic examination showed occlusion of the renal artery with organization, and the presence of a necrotic arterial wall with fibrosis, inflammation, and intact internal elastic lamina. Conclusions The RF electrode catheter/guide wire system successfully coagulated egg white and occluded the rabbit renal artery.

In Vivo Assessment of Chitosan/β-Glycerophosphate as a New Liquid Embolic Agent

We sought to assess the feasibility of using thermosensitive chitosan/β-glycerophosphate forembolotherapy. The renal arteries in nine rabbits were embolized with chitosan/β-glycero-phosphate. The animals were studied angiographically and sacrificed at one week (n = 3), four weeks (n = 3), and eight weeks (n = 3) after embolotherapy. Histology was obtained at these three time points. Delivery of chitosan/β-glycerophosphate was successful in all cases. Complete occlusion was achieved in all cases. No recanalization was observed in the follow-up angiograms. No untoward inflammatory reactions were observed in the target renal arteries and infarcted kidneys during the histological examinations. Our preliminary feasibility evaluation in rabbit renal arteries indicates that C/GP is a satisfactory embolization agent.

Differential vasodilation response to olprinone in rabbit renal and common carotid arteries

Olprinone, one of the most frequently used phosphodiesterase-3 inhibitors, exerts its positive inotropic and vasodilation effects by inhibiting the degradation of intracellular cyclic adenosine monophosphate (cAMP). The vasodilation response to olprinone is not uniform among the different vascular beds. This study was designed to compare the vasorelaxation response to olprinone between renal and common carotid arteries, and investigate its underlying mechanisms. Isometric force measurement, enzyme immunoassay, and western blotting techniques were used to investigate the vasorelaxation action of olprinone in isolated rabbit renal and common carotid arteries. Olprinone inhibited the contractile response to phenylephrine (PE) both in the renal and carotid arteries in a concentration-dependent manner with IC50 values of 40 +/- 10 and 103 +/- 43 nM, respectively. The IC50 value was lower (P = 0.004) and the maximal inhibition was greater (P = 0.002) in the renal artery compared with the carotid artery. A cell-permeable cAMP analogue, 8-bromo-cAMP, also inhibited the contractile response to PE in the renal and carotid arteries with IC50 values of 581 +/- 150 and 740 +/- 179 microM, respectively; however no differences were observed both in the IC50 value and the maximal inhibition between two arteries. Olprinone (0.1 microM) increased the intracellular cAMP level in the renal arterial smooth muscle cells (ASMCs) but not in the carotid ASMCs. The expression of PDE3A was greater (P = 0.008) in the carotid ASMCs than the renal ASMCs. The enhanced vasodilator action of olprinone in the renal artery is presumably because of its ability to stimulate the cAMP production, which might be attributable to the heterogeneous expression of PDE3A.

Mechanisms involved in the relaxant action of testosterone in the renal artery from male normoglycemic and diabetic rabbits

Kidney disease is a frequent complication in diabetes, and significant differences have been reported between male and female patients. Our working hypothesis was that diabetes might modify the vascular actions of testosterone in isolated rabbit renal arteries and the mechanisms involved in these actions. Testosterone (10 −8 to 10 −4 M) induced relaxation of precontracted arteries, without significant differences between control and diabetic rabbits. Both in control and diabetic rabbits endothelium removal inhibited testosterone relaxant action. In arteries with endothelium, incubation with indomethacin (10 −5 M), N G-nitro- l-arginine (10 −5 M) or tetraethylammonium (10 −5 M) did not modify relaxations to testosterone neither in control nor in diabetic rabbits. In endothelium-denuded arteries indomethacin enhanced the relaxant action of testosterone, both in control and diabetic rabbits. In arteries from diabetic rabbits, eNOS, iNOS and COX-1 expression and testosterone-induced release of thromboxane A 2 and prostacyclin were not significantly different from those observed in control rabbits. However, COX-2 expression was significantly lower in diabetic rabbits that in control rabbits. In nominally Ca 2+-free medium, cumulative addition of CaCl 2 (10 −5 to 3 × 10 −2 M) contracted previously depolarized arteries. Testosterone (10 −4 M) inhibited CaCl 2 contractions of the renal artery both in control and diabetic rabbits. These results show that testosterone relaxes the renal artery both in control and diabetic rabbits. This relaxation is modulated by muscular thromboxane A 2, it is partially mediated by endothelial prostacyclin, and it involves the blocking of extracellular Ca 2+ entry. Diabetes does not modify the mechanisms involved in the relaxant action of testosterone in the rabbit renal artery.