Interactions between extracellular and intracellular administered angiotensin II in isolated rat portal vein rings

It is already demonstrated that intracellular angiotensin II (Ang II) stimulates smooth muscle contraction and cell growth. We studied the contractile effects of Ang II intracellular delivered by the means of liposomes (LAngII) and also the interactions between intracellular and extracellular administered Ang II on the rat portal vein rings without endothelium. The results were expressed as the percentages of the control contraction (K+ 40 mM; mean +/- S.E.M). LAngII induced contractions were of 120.46 +/- 8.06%. On the other hand, 0.1 microM Ang II produced contractions of 121.43 +/- 6.83%. Both Ang II and losartan, administered either extracellular in the organ bath or intracellular by the means of liposomes, inhibited the contractions induced by intracellular Ang II. The inhibitory effects of losartan on LAngII-induced contractions were dose-dependent. Thus, 10 microM losartan strongly blocked (10.01 +/- 1.41%) and 1 microM losartan partially blocked (39.73 +/- 5.35%) the LAngII-induced effects. LLOS significantly inhibited the LAngII contractile effects (38.51 +/- 8.92%). Our results revealed that LAngII partially inhibited the contractions induced by extracellular administered Ang II (42.42 +/- 3.29%). On the other hand, 0.1 microM Ang II also inhibited the contractile effects induced by LAngII (67.42 +/- 0.76%), although a little bit less. So, contractions induced by Ang II administered intracellular are mainly mediated by intracellular Ang II receptors sensitive to losartan. At the same time, the participation of cell membrane angiotensin receptors to intracellular Ang II effects cannot be excluded.     

Responses of human gastroepiploic arteries to vasoactive substances: comparison with responses of internal mammary arteries and saphenous veins.

We examined the responses of human gastroepiploic arteries to histamine, serotonin, and norepinephrine, comparing those of internal mammary arteries and saphenous veins. Fresh specimens of the vessels were obtained intraoperatively from 21 patients. The vessels were suspended in organ chambers to record isometric tensions. With gastroepiploic arteries, histamine induced relaxations in the endothelial rings (85% +/- 7%) but failed to induce any contractions or relaxations in the rings without endothelium. The relaxations were prevented by methylene blue or hemoglobin and the H1-histaminergic receptor antagonist chlorpheniramine. With internal mammary artery rings with endothelium, histamine at a low concentration (10(-8) to 10(-5.5) mol/L) induced relaxations (53% +/- 12%) but evoked contractions at a higher concentration (10(-5) to 10(-4.5) mol/L). With saphenous veins, histamine caused only contractions. Serotonin induced markedly greater contractions in saphenous veins than in either artery. The endothelium inhibited the maximal contraction in response to serotonin in both arteries but not in veins. With the gastroepiploic artery, the responses to norepinephrine and serotonin were similar to those of the internal mammary artery. Histamine induces endothelium-dependent relaxations only, and histaminergic receptors that induce contractions may be absent on vascular smooth muscle cells. These vasoactive properties may contribute to the high patency as a coronary graft.     

Angiotensin II receptor modulation of renal vascular resistance and neurotransmission in young and adult spontaneously hypertensive rats

BACKGROUND/AIMS: Angiotensin (Ang) II modulates vascular resistance and sympathetic neurotransmission through Ang II type 1 (AT1) receptors. Recent studies reported an involvement of AT2 receptors. We investigated whether AT2 receptors participate in modulation of vascular resistance and sympathetic neurotransmission in spontaneously hypertensive rats (SHR). METHODS: Kidneys of 6- and 16-week-old normotensive (WKY) and SHR were isolated and perfused. RESULTS: Noradrenaline release induced by renal nerve stimulation (RNS) was increased in SHR (WKY: 1,837 +/- 128, SHR: 2,310 +/- 192 pg/g). Ang I- and II-induced pressor responses and enhancement of noradrenaline release were greater in SHR than in WKY. Pressor responses to Ang I and II were greater in adult compared with young SHR. The AT1 receptor antagonist EXP3174 (0.1 microM) blocked Ang I- and II-induced renal vasoconstriction and noradrenaline release to RNS in both strains. In contrast, the selective AT2 receptor antagonist PD 123319 (1 microM) had no influence in young and adult WKY and SHR. CONCLUSION: Ang I and II had a greater impact on renal vascular resistance and neurotransmission in SHR, which was more pronounced in adult SHR. All effects are mediated by the AT1 receptor and no modulatory influence of the AT2 receptor could be found.     

Kinetics of Altered Angiotensin II Responses in Experimental Vein Grafts

Following vein grafting. responses in the arterial vein bypass grafis to angiotensin II, a known mitogen, increase. It is not known when these changes occur or whether these changes are due to alterations in endothelial cell function, excision/imphtation of the vessel, or exposure to arterial hemodynamics. Two studies were designed to examine these questions. New Zealand White rabbits underwent excision of the external jugular vein, common carotid artery, an external jugular veno-venous bypass (VVG), or a common carotid veno-arterial bypass (VAG). Half the jugular veins and carotid arteries were mechanically denuded of their endotheliwn. All vein grafts were harvested at 28 days. A set of VAG was also harvested at 1, 3, 7, and 14 days. Isometric tension studies to angiotensin II (10-¹⁰ to 10-⁴ M) were performed on rings from each jugular vein, carotid artery, and vein graft. Jugular veins had a triphasic response to angiotensin II. Deendothelialized jugular veins had a triphasic response with an increased first phase and a much reduced second phase. Carotid arteries (6.87 ± 0.18 and 6.15 ± 0.18; with and without endothelium; means ± SEM,-log₁₀, [EC₅₀]; p <. 05), VVG (6.69 ± 0.15). and VAG (7.42 ± 0.29; p <. 05 compared to VVG) showed a monophasic response to angiotensin II at 28 days. This monophasic response in VAG to angiotensin II was recordable at 7 days postoperatively and there was no further change in its sensitivity between 14 and 28 days. These results suggest that the induction of altered angiotensin II responses is dependent on exposure to the arterial circulation, that alterations in VAG responses occur within the first 7 days of vein grafting, and that VAG at 28 days become more sensitive to angiotensin II than the carotid vessels into which they are placed. These changes in smooth muscle cell sensitivity to a known smooth muscle cell mitogen (angiotensin II) may contribute to the development of intimal hyperplasia in the veno-arterial graft     

Aging effects on contractility of longitudinal and circular detrusor and trigone of rat bladder.

PURPOSE: Aging is associated with bladder dysfunction, including difficult voiding and urinary leakage. Voiding involves reduction in the bladder lumen in all dimensions brought about by contraction of the meshwork of longitudinal, circular and oblique layers of detrusor smooth muscles. Most in vitro physiological studies of the effects of aging on bladder function used the longitudinal detrusor. To understand the region specific effects of aging on bladder function the contractile responses of longitudinal and circular detrusor, and trigone segments of the bladder from young and old rats were monitored. MATERIALS AND METHODS: These studies were performed using male Fisher 344 rats 6 months (young) and 27 months (old) old obtained through the National Institute on Aging. Each rat was anesthetized and the bladder was isolated. From each bladder a strip of longitudinal detrusor, circular detrusor and trigone was isolated and mounted in an in vitro multi-muscle chamber containing normal physiological solution at 37C. Isometric contractions of the 3 bladder strips were monitored after electrical field stimulation, 120 mM. potassium and 1 to 1,000 microM. bethanechol using a digital oscilloscope. RESULTS: In longitudinal detrusor from old rats there was no significant difference in the contractions evoked by electrical stimulation or high potassium but there was a significant reduction in contractions evoked by bethanechol compared with the responses of longitudinal detrusor from young rats. In circular detrusor from old rats there was a significant increase in contractions evoked by electrical stimulation and a slight increase in contractions produced by high potassium but no significant change in contractions evoked by bethanechol compared with the responses of circular detrusor from young rats. In trigone from old rats there was a significant decrease in contractions evoked by electrical stimulation, high potassium and bethanechol compared with young trigone. CONCLUSIONS: The reduction in contractions evoked by bethanechol suggests an age related reduction in muscarinic receptors in the longitudinal detrusor of aged rats. An increase in contractions evoked by electrical stimulation without a change in contractions evoked by bethanechol suggests a decrease in compliance caused by an increase in collagen in the circular detrusor of aged rats. A general decline in all contractile responses, including those evoked by high potassium, suggests reduced membrane depolarization in the trigone of aged rats. The effect of aging is specific to different regions and functional components of the bladder, probably due to changes in muscarinic receptors, collagen and depolarization.     

Effect of dexamethazone on hepatic vascular response in experimental sepsis

BACKGROUND: The aim of the present study was to evaluate the effect of dexamethasone-pretreatment on the hepatic artery and portal vein of septic rats, which were generated by lipopolisaccarides (LPS) intraperitoneal injection. METHOD: Thirty-six albino Wistar rats were used and constructed as LPS (n = 12), control (n = 12), dexamethazone-pretreatment (n = 6) and dexamethazone-control (n = 6) groups. Hepatic artery and portal vein rings were excised and placed in Krebs-Henseleit solution. Vessel rings were contracted with phenylephrine adding to the organ chamber in cumulative doses. Then the contraction-response curves were drawn. RESULTS: In the LPS group, phenylephrine evoked contractions were reduced in both hepatic artery and portal vein rings in comparison to the control group. In the dexamethasone-control group, phenylephrine-evoked contractions were increased but not significantly. Dexamethasone-pretreatment increased the phenylephrine-evoked contractions close to the values of control group for both types of rings. CONCLUSIONS: Dexamethasone pretreatment corrected the vascular hyporeactivity to phenyleprine in isolated portal vein and hepatic artery rings prepared from the LPS treated rats in experimental sepsis. This might have occurred as a result of inhibition of inducible nitric oxide synthase expression.     

Renal responses to AT1 blockade in angiotensin II-induced hypertensive rats.

Previous studies have shown that uninephrectomized rats infused chronically with low doses of angiotensin II (Ang II) develop progressive hypertension that is prevented by coadministration of losartan in the drinking water. The present study was performed to contrast the effects of chronic and acute losartan treatment in reversing the Ang II-mediated actions on arterial pressure and renal function. Ang II was infused subcutaneously via osmotic minipumps (40 ng/min) for 13 days in two groups (N = 10 and N = 6); one group also received losartan in the drinking water (30 mg/kg.day) throughout this period. Untreated rats (N = 6) and rats (N = 6) receiving only losartan served as control groups. Ang II-infused rats had higher mean arterial pressures (153 +/- 7 versus 107 +/- 3 mm Hg) and lower GFR (0.7 +/- 0.04 versus 0.98 +/- 0.06 mL/min.g) than Ang II-infused rats receiving losartan chronically. The Ang II-infused rats responded to acute doses of losartan (10 mg/kg) with progressive reductions in arterial pressure and significant increases in cortical blood flow (34 +/- 12% increase), renal plasma flow, GFR, and sodium excretion; however, the increases in renal blood flow and GFR were not sustained as systemic arterial pressure decreased. Because Ang II-infused rats receiving losartan chronically still exhibited decreases in RBF in response to a bolus dose of Ang II, further studies evaluated the effects of acute losartan treatment in rats treated chronically with losartan. Although arterial pressure decreased only slightly, demonstrating adequate systemic vascular blockade, there were still substantial and sustained increases in renal plasma flow, cortical blood flow (20 +/- 4% increase), GFR, and sodium excretion. In summary, the modest responses to acute losartan in Ang II-infused rats indicate that chronic Ang II infusions lead to alterations in renal function that are only partially reversible by acute losartan treatment. In contrast, chronic treatment with losartan prevents the Ang II-induced decrease in GFR. The renal responses to acute losartan in the Ang II-infused rats treated chronically with losartan suggest that substantive intrarenal actions of Ang II can be maintained even when the systemic vascular AT1 receptors are effectively blocked.     

Halothane 1.5 MAC, isoflurane 1.5 MAC, and the contractile responses of coronary arteries obtained from human hearts

Active vasoconstriction of epicardial coronary arteries can cause myocardial ischemia in patients with coronary artery disease. Relief of vasoconstriction can improve blood flow to the heart. The purpose of this study was to determine if 1.5 MAC halothane and 1.5 MAC isoflurane would each attenuate contractions evoked by three putative mediators of coronary constriction in coronary arteries removed from the hearts of human beings. Hearts were obtained in the operating room from five patients undergoing cardiac transplantation and from six brain-dead patients undergoing organ donation procedures. Coronary arteries were dissected free, cut into rings, and studied in organ chambers. Endothelium-dependent relaxations to 10(-6) M bradykinin were examined; they indicated a variable degree of endothelial dysfunction in vessels used in the experiments. Contractile responses to 40 mM KCl were tested and were used as control contractions. Contractions evoked by serotonin, histamine, and prostaglandin F2 alpha were measured and were expressed as a percent of contractile responses evoked by 40 mM KCl. Halothane depressed the agonist-induced contractions. Maximal contractile responses to serotonin were 130% +/- 28% in untreated rings and 63% +/- 10% in rings exposed to halothane (P less than 0.03). Responses to histamine were 183% +/- 46% untreated and 121% +/- 26% during halothane administration (P less than 0.05), and responses to prostaglandin F2 alpha were 227% +/- 42% untreated and 148% +/- 18% with halothane (P less than 0.05). Isoflurane had no effect on contractions. The results demonstrate that 1.5 MAC halothane, but not 1.5 MAC isoflurane, attenuates contractile responses evoked by putative mediators of coronary vasoconstriction in coronary arteries removed from the hearts of human beings.     

Effects of angiotensin-(1-7) blockade on renal function in rats with enhanced intrarenal Ang II activity

BACKGROUND: Increasing evidence suggests that angiotensin-(1-7) [Ang-(1-7)] acts as an endogenous antagonist of Ang II when the renin-angiotensin system (RAS) is activated. In the present study, we therefore compared the effects of acute intrarenal (i.r.) Ang-(1-7) receptor blockade on renal function under conditions of normal and increased intrarenal Ang II concentration. METHODS: Salt-replete Hannover-Sprague Dawley rats (HanSD) served as control animals. As models with enhanced action of Ang II we first used transgenic rats harboring the Ren-2 renin gene (TGR), second, Ang II-infused rats, third, 2-kidney, 1-clip (2K1C) hypertensive rats on normal salt intake, and fourth, salt-depleted TGR and HanSD. RESULTS: I.r. Ang-(1-7) receptor blockade elicited significant decreases in glomerular filtration rate (GFR), renal plasma flow (RPF), and sodium excretion in 2K1C rats, and in salt-depleted TGR and HanSD. In contrast, i.r. Ang-(1-7) receptor blockade did not significantly change GFR, RPF, and sodium excretion in salt-replete TGR and HanSD, or in Ang II-infused rats. CONCLUSION: These findings suggest that under conditions of normal intrarenal RAS activity and increased intrarenal Ang II action by infusion of Ang II or by insertion of a renin gene in salt-replete conditions, Ang-(1-7) is not an important factor in the regulation of renal function. In contrast, under conditions of endogenous RAS activation due to clipping of the renal artery or to sodium restriction, Ang-(1-7) serves as opponent of the vasoconstrictor actions of Ang II.     

Production of endothelium-dependent relaxation responses by saphenous vein grafts in the canine arterial circulation

To determine if venous endothelium can acquire the ability to elicit endothelium-dependent relaxation responses, five dogs underwent femoral artery bypass with autogenous saphenous vein. The veins were harvested 15 to 17 months later. Endothelium-dependent relaxation was determined by measuring tension of deendothelialized coronary arteries mounted on a tensiometer and superfused with the effluent of the vein grafts. These grafts were perfused with acetylcholine and calcium ionophore A23187, which cause case vascular smooth muscle relaxation by means of endothelium-dependent relaxing factor production. Control arteries and veins were obtained from other dogs for comparison. In response to acetylcholine from 10(-9) to 10(-4) mol/L, the final cumulative relaxation produced in the detector coronary artery (mean +/- SD) was 64.2% +/- 25.7% by the control arteries, 14.2% +/- 5.5% by the vein bypass graft, and 5.3% +/- 5.6% by the control veins. In response to A23187 from 10(-8) to 10(-4) mol/L, the final cumulative relaxation was 66.2% +/- 19.0% by the control arteries, 30.6% +/- 8.9% by the vein bypass grafts, and 5.3% +/- 5.6% by the control veins. The differences were significant between the vein bypass grafts and the control arteries (p less than 0.04 for acetylcholine; p less than 0.04 for A23187) and the control veins (p less than 0.03 for acetylcholine; p less than 0.02 for A23187). Perfusion of saphenous veins used as chronic arterial bypass grafts with either acetylcholine or A23187 produced detector vessel relaxation, consistent with endothelium-dependent relaxing factor production. The magnitude of the relaxation response did not approach that from perfusion of control arteries.     

Contractile effects of angiotensinogen and its multiple metabolization pathways on vessel walls

The contractile effects of angiotensinogen (Aogen) and its metabolization pathways were studied on rat renal vein (RRV), rat pulmonary artery (RPA) and human umbilical vein (HUV) rings. Experiments were made in the presence or in the absence of pepstatin A (a renin inhibitor, 10 microM), captopril (an ACE inhibitor, 10 microM), chymostatin (a chymase inhibitor, 10 microM), amastatin (an aminopeptidase-A and -M inhibitor) or losartan (a specific AT1 blocker, 10 microM). On all rings, Aogen-induced contractions were reduced by pepstatin A or captopril, amplified by amastatin and blocked by losartan. Chymostatin had a stronger inhibitory effect than captopril on HUV and simultaneous administering of chymostatin and captopril prevented Aogen contractile effects on HUV. It is suggested that all studied vessels possess a local renin-angiotensin system and possibility of angiotensin II production within the vessel walls using various and species-dependent enzymatic pathways.     

后腹腔镜下肾切除应用威克外科结扎锁处理肾动静脉可靠性分析

目的:探讨后腹腔镜下肾切除应用威克外科结扎锁处理肾脏动静脉的可靠性.方法:124例后腹腔镜肾切除,采用腰部3个Trocar(2个10 mm,1个5 mm),由腹膜外人路.根据肾动脉搏动找到并分离出肾动脉,游离肾动脉至适当长度,用13 mm威克外科结扎锁(Hem-o-lok,Week Closure Systems)处理肾动脉,肾动脉近心端以2枚夹闭,远心端以1枚夹闭.切断肾动脉,同法处理肾静脉.结果:124例均顺利完成手术,动静脉处理过程顺利、安全,所有病例均用威克外科结扎锁处理完成,无结扎锁滑脱现象,术中及术后未出现继发性出血,术中出血10～100 ml,平均45 ml,均未输血,术后平均住院日6.5天.结论:后腹腔镜肾切除应用威克外科结扎锁处理肾脏动静脉安全、可靠、经济、操作方便.     

Clinical research of renal vein control using Hem-o-lok clips in laparoscopic nephrectomy

Control of the renal vein represents a crucial step in laparoscopic nephrectomy. Although endovascular gastrointestinal anastomosis (GIA) staplers have generally been used for renal vein control because of the large diameter of the vessel, Hem-o-lok clips have recently been used for renal artery control. GIA staplers are expensive and can malfunction on rare occasions, resulting in severe complications. We evaluated renal vein control using Hem-o-lok clips (adaptive vascular width 7-16 mm) in laparoscopic nephrectomy. Since April 2004, we have ligated renal arteries using Hem-o-lok clips. From June 2004, this method was applied for renal vein control in 40 laparoscopic nephrectomies. After renal pedicle dissection, renal pedicle ligation was accomplished using extra large (XL) Hem-o-lok clips on both the renal arteries and veins by placing two clips on the patient side and one clip on the specimen side. Ligation times for obtaining renal vein control were compared between XL Hem-o-lok clips and GIA staplers in 40 cases before June 2004. Vascular control using XL Hem-o-lok clips was successful in all 40 cases, without any slipping of clips or uncontrolled bleeding. After renal pedicle dissection, ligation time for achieving renal vein control was 167.0 +/- 48 s (range: 122-295 s) using XL Hem-o-lok clips (mean, three clips) and 68 +/- 24.0 s (range: 54-150 s) using a GIA stapler. XL Hem-o-lok clips allow safe and reliable control of renal veins in laparoscopic nephrectomy. Ligation time is only 100 s longer than using a GIA stapler. In addition, costs are reduced by more than 90% compared to GIA stapling.     

Comparison of prazosin, terazosin and tamsulosin: functional and binding studies in isolated prostatic and vascular human tissues

BACKGROUND: Terazosin and tamsulosin are drugs currently used in the treatment of benign prostatic hypertrophy (BPH). The potency of these two alpha(1) receptor antagonists and that of prazosin to inhibit contractions induced by noradrenaline and the binding of [(3)H]-prazosin in human prostate and four different human arterial and venous vessels (saphenous and umbilical veins, renal and mesenteric arteries) was studied. METHODS: By bioassay and binding studies, we examined the receptor affinities of different alpha(1) receptor antagonists in different human tissues. RESULTS: pKb of terazosin, tamsulosin, and prazosin obtained in the prostatic tissues (8.15, 9.64, and 8.59, respectively) were not different from those obtained in the umbilical veins (8.07, 9.56, and 8.30, respectively), in the mesenteric artery (8.27, 10.29, and 9.01, respectively), renal artery (8.35, 10.13, and 8.76, respectively) and saphenous vein (7.8, 10.3, and 9.32, respectively). IC(50) (nM) of prazosin, terazosin, and tamsulosin obtained from binding studies in membrane preparations from prostate tissue were similar to those from umbilical veins, saphenous vein, and renal artery. CONCLUSIONS: All of the evaluated drugs showed similar selectivity for prostatic vs. vascular tissues. Thus, different clinical profiles of the present drugs should not result from their differential affinity for prostatic versus vascular alpha(1)-adrenoceptors.     

Endothelium-dependent vasorelaxations in response to aggregating platelets are impaired in reversed vein grafts

The endothelium releases factor(s) that are potent vasodilators and inhibitors of platelet aggregation. Experiments were performed to determine whether the endothelium-dependent responses to aggregating platelets are altered in vein grafts. Segments of jugular veins were grafted in the reverse position into the carotid arteries in 16 rabbits. After 4 weeks the patent grafts (14 of 16) were removed, and the endothelium-dependent responses were examined in vitro. In control veins aggregating platelets, adenosine diphosphate, and serotonin caused endothelium-dependent relaxations. The platelet-induced relaxations were attenuated by apyrase (adenosine diphosphatase and adenosine triphosphatase) but not by methiothepin (serotonergic blocker). In vein grafts, endothelium-dependent relaxations in response to aggregating platelets were absent, and only contractions that could be attenuated by methiothepin were observed. In vein grafts, endothelium-dependent relaxations in response to adenosine diphosphate were reduced, and only endothelium-independent contractions were observed in response to serotonin. These contractions were attenuated by methiothepin. These results suggest that (1) the endothelium exerts an inhibitory effects mediated mainly by adenosine diphosphate in response to aggregating platelets in rabbit jugular veins and (2) endothelium-dependent relaxations in response to aggregating platelets are impaired in vein grafts because of reduced endothelium-independent contractions in response to serotonin. This impairment of endothelium-dependent responses in vein grafts may contribute to failure of the grafts.     

Effects of vasoactive agents in healthy and diseased human saphenous veins

Purpose: Smooth muscle reactivity is one of the factors involved in the pathogenesis of varicose veins. We investigated the myotropic effects of the 3 main vasoconstrictor agents—norepinephrine (NE), angiotensin II (Ang II), and endothelin-1 (ET-1)—in isolated human saphenous veins. Methods: Human saphenous veins were collected from 23 patients with primary chronic venous insufficiency who underwent elective varicose vein resections and who were stratified into the following 3 groups: group 1, 7 patients in clinical class 2; group 2, 9 patients in clinical classes 3 and 4; and group 3, 7 patients in clinical classes 5 and 6. Moreover, 6 patients who underwent arterial bypass grafting procedures represented the control group. The tissues were suspended in organ baths that contained Krebs solution, and their mechanical responses were measured isometrically. The cumulative concentration–response curves to Ang II, NE, and ET-1 were performed at 90-minute intervals in each tissue. Results: In the control tissues, NE, Ang II, and ET-1 induced concentration-dependent contractions with apparent affinities (pEC₅₀, the negative logarithm to base 10 of the molar concentration of the agonist, which produces the 50% of the maximal effect) and maximal effects (maximum effect, g of contraction) that were equal to 7.06 ± 0.23, 8.53 ± 0.34, 7.63 ± 0.10, and 2.21 ± 0.33, 1.65 ± 0.31, 2.60 ± 0.77, respectively. Two main findings were evident in comparison of varicose veins with control tissues. First, the maximum effect that was evoked by all of the stimulants was reduced progressively with the increasing severity of the disease, which raised the third group to statistical significance for both NE and Ang II (P < .05). Second, a marked reduction of Ang II apparent affinity was already evident in tissues that were taken from patients in an early stage of the disease (P < .05). Conclusion: The demonstration of a significant reduction in Ang II and NE contractile activities and the important reduction of that of ET-1 in the diseased veins as compared with the control tissues extends the previous observations regarding the impairment of smooth muscle contractility in primary chronic venous insufficiency. Moreover, the dramatic reduction of Ang II affinity, which appears in an early stage of the disease, supports the hypothesis that such abnormality within the venous wall could play a role in the pathogenesis of primary varicose vein disease. (J Vasc Surg 1998;28:855-61.)     

Angiotensin II type 1 receptor gene polymorphism predicts response to losartan and angiotensin II

Angiotensin II type 1 receptor gene polymorphism predicts response to losartan and angiotensin II. BACKGROUND: Most of the known actions of angiotensin II (Ang II) are mediated by the Ang II type 1 receptor (AGT1R). A noncoding polymorphism of the AGT1R gene has been described in which there is either an adenine (A) or cytosine (C) base at position 1166. The functional significance of this polymorphism is unknown, prompting us to examine the relationship between this polymorphism and the systemic and renal responses to AGT1R blockade and subpressor Ang II infusion. METHODS: Sixty-six healthy Caucasian men and women, genotyped for the AGT1R polymorphism by polymerase chain reaction, were chosen to form two homogeneous groups: AA and AC/CC. Renal hemodynamic function was assessed with inulin and para-aminohippurate clearance before and after AGT1R receptor blockade with losartan and Ang II infusion. RESULTS: The mean values at baseline for glomerular filtration rate (GFR), renal plasma flow (ERPF), and renal blood flow (RBF) were significantly lower in the AC/CC group compared with the AA group. Losartan increased the GFR and decreased the mean arterial pressure (MAP) in the AC/CC group, but did not influence these parameters in the AA group. The aldosterone responses to losartan were blunted in the AA subgroup. During Ang II infusion, AC/CC subjects maintained GFR despite equivalent declines in RBF, suggesting an enhanced efferent arteriolar constrictive response. CONCLUSIONS: Taken together, these results suggest that there is a relationship between the AGT1R A1166-->C polymorphism and the humoral and renal hemodynamic responses to AGT1R blockade and to Ang II infusion in the sodium-replete state, and that the C allele is associated with enhanced intrarenal and peripheral Ang II activity. Further studies are required to determine the genetic locus for this effect.     

Ultrasound imaging findings of femoral veins in patients with renal failure and its impact on vascular access.

BACKGROUND: Patients requiring dialysis due to acute or chronic renal failure frequently require temporary vascular access. Femoral vein catheterization is the easiest method for obtaining temporary vascular access in haemodialysis patients. The aim of this study was to utilize ultrasound imaging to describe femoral vein structures and to examine anatomical variations in uraemic patients. METHODS: We evaluated 114 (70 males, 44 females) renal failure patients. Femoral arteries were localized manually inferior to the femoral ligament, and ultrasonographic examination was performed from this location. Images of the vessels and demographic data of patients were recorded and analysed. Femoral veins were classified according to their diameter, patency and palpation status of the neighbouring femoral artery. RESULTS: Three patients had a history of prior femoral catheterization. In one of these, who had a history of bilateral catheterization, we detected bilateral femoral vein thrombosis. Overall, non-palpable femoral arteries or unsuitable femoral veins were found unilaterally in 16 patients (14.0%) and bilaterally in six patients (5.2%). The depth of femoral arteries (r = 0.54, P<0.001) and femoral veins (r = 0.59, P<0.001) was correlated with body mass index (BMI). Femoral arteries and femoral veins were located significantly deeper in overweight (BMI >25) patients compared with normal weight patients (20.7+/-6.5 vs 14.6+/-5.1 mm, P<0.001 and 26.1+/-6.7 vs 18.9+/-5.5 mm, P<0.001). CONCLUSIONS: Bilateral anatomical variations of femoral veins were relatively rare. However, ultrasound surveys should be performed in obese patients or when the femoral artery is not palpable.     

Effects of propofol and thiopental in isolated rat aorta and pulmonary artery.

This study was performed to determine if direct arterial dilating actions of propofol contribute to the drug's hypotensive actions. The effects of propofol were compared with those of thiopental on isolated vascular ring preparations from rat thoracic aorta and pulmonary artery. Thoracic aortic ring responses were evaluated in the presence and absence of endothelium, indomethacin, and N omega-nitro-L-arginine methyl ester (LNAME; a specific inhibitor of endothelium-derived relaxing factor-nitric oxide [EDRF/NO] synthase). Pulmonary artery responses were investigated with intact endothelium. After the induction of active isometric force by a predetermined EC50 dose of phenylephrine for each ring, effects of propofol (30, 100, 300 microM) and thiopental (10, 30, 100 microM) were examined. Propofol caused significant vasodilation in endothelium-intact, endothelium-denuded, and LNAME-treated aortic rings. In the endothelium-intact aortic and pulmonary artery rings, the initial vasodilation due to 30 and 100 microM propofol showed gradual and partial recovery over 15 min; 300 microM propofol caused sustained vasodilation. Endothelium-denuded rings and LNAME-pretreated endothelium-intact rings showed constant and sustained vasodilation with all propofol concentrations. Propofol also caused marked vasodilation in pulmonary arteries. In contrast, thiopental had no vasodilating effect in aortic or pulmonary artery preparations. In control experiments, propofol vehicle (Intralipid) also had no effect on vascular rings. Indomethacin pretreatment induced a dose-dependent vasoconstriction by thiopental in endothelium-intact rings and decreased the vasodilation due to propofol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of stretch or distention on phenylephrine-induced constriction of human coronary artery bypass grafts

OBJECTIVE: To determine the effects of grafting saphenous veins into the arterial circulation and to compare the responsiveness of saphenous veins and mammary arteries to vasoconstrictors (phenylephrine or potassium) and a vasodilator (the calcium antagonist isradipine). DESIGN: Prospective, controlled, in vitro study. SETTING: Laboratory facility in a university teaching hospital. PARTICIPANTS: Small excess segments of internal mammary arteries or saphenous veins obtained from patients undergoing coronary artery bypass graft surgery. INTERVENTIONS: Vessel segments were cut into rings to measure isometric tension development in isolated tissue chambers. The law of LaPlace for a cylinder was applied to determine tensions in vitro corresponding with arterial or venous tensions in vivo or distending pressures ex vivo. MEASUREMENTS AND MAIN RESULTS: Stretching saphenous vein rings from venous to arterial tensions reduced maximal phenylephrine-induced constriction but did not alter their dose response to phenylephrine, potassium, or isradipine. At arterial tensions, potassium, but not phenylephrine, was more potent in constricting mammary artery than saphenous vein; isradipine was more potent as a vasodilator of potassium-constricted mammary artery than saphenous vein. Maximal phenylephrine-induced or potassium-induced constriction was no different for either vessel at arterial tensions; however, prior distention of veins to tensions corresponding with pressures of 200 or 300 mmHg significantly (p < 0.01, Dunnett's test) reduced subsequent constriction. CONCLUSION: Phenylephrine may be more likely to constrict native internal mammary arteries than distended autogenous saphenous vein grafts in vivo because high-pressure distention of veins markedly inhibits their vasoreactivity.