Significant Difference In Relaxation Research Articles

Vitamin D deficiency in diabetes alters the aortic media thickness but not its functional properties

This study aimed to determine the effects of a vitamin D deficiency on aortic functional and structural properties in diabetic rats. Diabetic rats were induced with 50 mg/kg streptozotocin and divided into two equal groups: diabetic rats on a normal diet (DR) and diabetic rats on a vitamin D-deficient diet (DRD). Non-diabetic rats that received a normal diet were the controls (CR). At the end of 10 weeks, rats were sacrificed and aortic rings with and without the endothelium were studied in tissue organ baths for isometric force measurements. Histology of aortic tissue was performed to determine the intima-media thickness. Serum levels of 25-hydroxyvitamin D in the DRD group were significantly decreased compared to the CR and DR groups. Acetylcholine-induced endothelium-mediated relaxation was significantly impaired in DR and DRD compared to CR. Endothelium-dependent contraction to calcium ionophore was significantly augmented in DR and DRD aortas compared to CR. The responses to acetylcholine and calcium ionophore were similar in DRD and DR. There were no significant differences in relaxation to sodium nitroprusside or contraction to phenylephrine between aortas of the groups. The intima-media thickness was significantly greater in the DR group compared to the CR group, and this structural change was augmented in aortas of the DRD group. In conclusion, this study showed that endothelial function was impaired with diabetes, and a vitamin D deficiency did not aggravate endothelial dysfunction. However, diabetes with a vitamin D deficiency demonstrated smooth muscle hypertrophy and an increased aortic media thickness.

English

BACKGROUND The selective alpha-blockers are widely used in the clinical treatment for ureteral stones as MET (Medical Expulsive Therapy). American Urological Association and European Association of Urology, strongly recommend that patients with ureteral stones be alpha-blockers to promote stone passage. Due to the physiological effect of alpha-blockers on the ureter, researchers hypothesized that the use of alphablockers before ureteroscopy may help during the Ureteroscopic procedures, making it easier and safer. One critical step in doing ureteroscopy is directing scope into vesicoureteral junction as most of the time its non-dilated and this is place injury and later stricture chances are high which lead to failure of treatment.3 But in literature, there is a discrepancy with this hypothesis as some studies have failed to demonstrate the benefits of technical ease and lower complication rate with alpha-blocker being used in the preoperative period. METHODS We conducted a cross sectional study in the department of urology from January 2019 to January 2020. 30 patients of ureteric calculus on alpha-blocker therapy and 30 patients of BPH on alpha-blocker ± 5 alpha reductase therapy were included for study. During URSL (Ureteroscopic Lithotripsy) we used 6 / 7.5 fr URS (Ureterorenoscope), ease of admitting URS in vesicoureteral junction noted. The need for ureteral dilator for admitting URS, presence of mucosal injury, and bleeding or false passage noted as difficulty in instrumentation. And documentation of finding done in excel. RESULTS Out of 60 patients, 24 (40 %) patients didn’t need dilatation of ureteric orifice and Ureteroscopy was done easily among which 8 (33.33 %) were BPH patient and 16 (66.66 %) were ureteric calculus patient this difference is statistically significant with p-value 0.010. 36 (60 %) patients needed dilatation of ureteric orifice to facilitate URS of which 22 (61.11 %) patients were from the BPH group and 14 (38.88 %) are ureteric calculus group. The study shows a statistically significant difference with p-value 0.029. CONCLUSIONS Our study demonstrates that alpha-blockers failed to show a statistically significant difference in relaxation of the ureteric orifice in non-ureteric calculus patients. Further large group, multi-centric studies are required to find a definitive role for alpha blockers prior to URS. KEYWORDS BPH, Silodosin, Ureteroscopy, Ureteric Orifice, Alpha Blocker, Alpha 1a, Medical Expulsion Therapy

PO-01-064 Testosterone relaxes human corpus cavernosum tissue of patients with erectile dysfunction

To investigate the effect of testosterone (T) on relaxation of human corpus cavernosum tissue. Human corpus cavernosum tissue samples were obtained after consent from men undergoing penile prosthesis implantation (n=46) for organ bath experiments. Tissue strips were precontracted with phenylephrine after which increasing doses of T, DHT, and androstenedione were added. Blockade of androgen receptor as well as hydrogen sulfide and nitric oxide biosynthesis was studied. Fifteen minutes after addition of the different compounds, tissue relaxation was measured. Results are expressed as mean+/-SD. Statistical analysis was performed using unpaired t-test. T relaxed precontracted tissues with 70.7+/-16.9 % (p = 0.003) at 300 microM compared to DMSO vehicle only. Addition of 300 microM of androstenedione (p = 0.17) and DHT (p=0.09) resulted in no significant difference in relaxation compared to T. Maximum relaxation response to T were not inhibited by N (G)-nitro-L-arginine methyl ester (p = 0.16), beta-cyanoalanine (p = 0.16), propargylglycine (p=0.34) and glibenclamide (p=0.73). The addition of 350 nanoM flutamide (androgen receptor inhibitor) did not alter the effect of T on tissue relaxation with 80.2 +/- 26.5% of relaxation compared to T alone (p = 0.25).

Effects of music therapy with patients on a post-surgical oncology unit: A pilot study determining maintenance of immediate gains

Researchers have found that music therapy can be an effective psychosocial intervention for oncology patients. However, due to shortened inpatient hospital stays and the frequency of surgery for patients with cancer, there is a need to determine maintenance of single-session treatment gains with patients on a post-surgical oncology unit. The purpose of this pilot study was to evaluate maintenance of immediate music therapy treatment gains concerning relaxation, pain, anxiety, nausea, and perception of music therapy with patients on a surgical oncology unit. Participants were adult oncology inpatients (n=27) and their caregivers (n=4) receiving care on a surgical oncology unit. Participants completed five separate 10-point Likert-Type Scales at pretest, posttest, and 30–45-min follow-up. Participants received 20-min music therapy sessions consisting of patient-preferred live music. Analyses of variance (ANOVA) were computed on all patient data and indicated significant differences in relaxation, anxiety, and pain between pretest and posttest and pretest and follow-up measures. However, there were no significant differences from posttest to follow-up, indicating maintenance of treatment gains. Although generalizations are premature due to the lack of a comparison condition, it seems that beneficial effects of a single music therapy session for surgical oncology patients may be maintained in the short-term. Limitations, implications for clinical practice, and suggestions for future research are offered.

Transmural Distribution of Myocyte Contractile Properties in Aging F344 Rats

Age-associated diastolic heart failure occurs when the amount of blood filling the heart between beats is reduced due to slow relaxation and increased passive stiffness of the left ventricle. We are testing the hypothesis that slowed active relaxation in diastolic heart failure is caused in part by age-dependent alterations in the contractile function of different transmural regions of the myocardium. Cardiac myocytes from endocardial, midmyocardial, and endocardial regions of the left ventricular free wall were isolated from hearts of 6, 18, and 22-month-old female Fischer 344 rats (n = 2 at each age). Cells were placed in a superfusion chamber controlled at 25oC and field stimulated at 0.5 Hz. Unloaded sarcomere shortening was measured in an average of 27 cells per myocardial region per animal. In five of the six animals, significant differences in relaxation (time from peak shortening to 50% re-lengthening, tp50) were observed among cell subtypes (p < 0.05, ANOVA). Analysis of collated data showed that tp50 was significantly affected by age, tending to increase in older animals (p < 0.01, two-way ANOVA). Aging appeared to have the greatest effect on relaxation of epicardial and midmyocardial cells.

Smoking Impairs Endothelial Function in Human Saphenous Vein in an Ex Vivo Model

The aim of this ex vivo experimental study was to assess the effect of smoking, diabetes mellitus, and hypertension on endothelial function in human saphenous vein, a commonly used conduit for coronary and peripheral arterial bypass surgery. A segment of long saphenous vein harvested during infrainguinal bypass surgery was mounted in an organ bath for isometric tension studies. Vein rings were precontracted to submaximal contraction with phenylephrine, followed by endothelium-dependent relaxation with acetylcholine. Long saphenous vein segments were collected from 26 patients, including five females, with a mean age of 66.4 years (range 48-92). Current smokers had impaired endothelium-dependent relaxation compared to ex- and nonsmokers (10.2%, n=13, vs. 32.9%, n=13; p<0.010). However, ex-smokers and nonsmokers did not have a significant difference in relaxant responses to acetylcholine (29.1%, n=8, vs. 24.6%, n=5; p=nonsignificant [ns]). Similarly, diabetic and nondiabetic patients did not show a significant difference in endothelium-dependent relaxation (23.1%, n=10, vs. 15.6%, n=16; p=ns). The relaxant responses in hypertensive and normotensive patients were not different (20.4%, n=12, vs. 22.5%, n=14; p=ns). Smoking has a deleterious effect on the endothelial function of saphenous vein, and smoking cessation may improve the long-term durability of saphenous vein used as a bypass graft in patients undergoing arterial reconstruction.

Direct effects of lead (Pb 2+) on the relaxation of in vitro cultured rat aorta to acetylcholine

Lead (Pb 2+) exposure is related to increased blood pressure or hypertension of human or animals. Abnormal vascular relaxant responses of low level Pb 2+ exposed animals were reported by several studies. However, it is difficult to tell whether these effects were induced directly by Pb 2+ or not. In this study we hypothesized that Pb 2+ can directly affect the relaxation of vessels. Male Wistar rat aortae were removed and cultured in PMRI 1640 with 1 ppm Pb 2+ (4.8 μM lead acetate) for 0.5, 6, 12 and 24 h, and then their responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were examined. After incubated for 24 h, the relaxation induced by ACh was significantly decreased in Pb 2+ exposed aortic rings. However, there was not significant difference in relaxation induced by SNP between Pb 2+ exposed and control group. The nitrite in the culture media of aortic rings cultured for 24 h, measured with Griess method, was significantly decreased in the Pb 2+ exposed group. The expression of endothelial NOS (eNOS) and isoform NOS (iNOS) in the homogenate of aortic rings cultured for 24 h was measured by Western blot. The expression of eNOS of the Pb 2+ exposed group was significantly upregulated compared with that of the control group. However, there was no significant difference in the expression of iNOS in control and Pb 2+ exposed group. In conclusion, Pb 2+ was able to directly affect the relaxation of rat aorta. This effect may have some relation with the lower level of NO in the media, though the expression of eNOS was upregulated.

비소 스트레스에 의한 흰쥐 대동맥의 수축과 이완반응의 변화양상

외부에서 가해진 비소 스트레스가 내피유무에 따른 흰쥐 대동맥의 수축력 증가와 이완반응에 미치는 영향을 알아보고자 본 실험을 실시하였다. 혈압의 측정은 생리기록계를 이용하였고, 내피 유무에 따른 혈관의 수축력은 Organ bath에 조직을 걸고 자동조절 생리기록계를 이용하여 측정하였다. 중추신경계를 파괴시킨 흰쥐의 생체 내 실험에서 비소처리로 vasopressin과 phenylephrine에 의한 혈관 수축력은 대조군에 비해 각각 19.1%와 46.6%로 대동맥의 혈압은 상승되었다. 0, 0.5, 1, 2 및 4 mM As을 처리한 적출 대동맥 실험에서 phenylephrine <TEX>$(10^{-6}M)$</TEX>을 가했을 때 5시간까지는 혈관 수축력의 변화가 미미했으나 8시간째 비소 처리군은 대조군에 비해 39% 증가된 값을 보여 수축력이 더욱 유의하게 증가되었다. 내피 제거 시 저농도 비소처리에서 다소 신속한 수축반응을 보였으나 고농도 비소 처리시에는 내피유무에 따른 차이가 유의적이지 않았다. 이완제 sodium nitroprusside와 acetylcoline를 처리했을 때 대조군에 비해 다소 증가된 이완력을 보였고, 시간경과에 따라 내피 비의존적인 nitroprusside와 달리 내피 의존적인 acetylcholine에서 이완력이 대조군에 비해 다소 촉진되었다. 이상의 결과에서 4 mM As처리시 혈관의 수축력은 증가되었으나 내피유무에 따른 차이는 유의적이지 않았고, 내피가 혈관의 이완력을 다소 촉진시킨 것으로 나타났다. 결론적으로 비소처리한 혈관은 내피유무와 무관하게 수축력이 증가되어 장기간 고농도 비소에 노출 시 고혈압을 유발할 우려가 있을 것으로 여겨진다. In order to examine whether arsenic, one of environmental stress, contribute to augumentation and relaxation of rat aorta, this study was performed in vivo and in vitro, using intacted or denuded rats aorta ring preparation, respectively. The carotid arterial pressure was recorded on an ink-writing physiograph(Grass Co. 79E) connected to strain gauge. The contractile response of vascular ring with or without endothelium preparation isolated from rat were determined in organ bath and was recorded on physiograph connected to isometric transducer. Vasopressin-,and phenylephrine- induced increase in arterial pressure significantly enhanced in arsenic-treated rats; increase of 19.1%, and 46.6%, respectively. Vascular contractile response was measured in vitro preparations exposed to 0, 0.5, 1, 2 and 4 mM of arsenic for 1, 3, 5 and 8 hours. The dose-vascular responses of phenylephrine augmented by increasing dose of arsenic in the strips exposed to arsenic for 8 hours, and did not augmented for 1, 3, 5 hours. The phenomenon was not affected by strips denuded endothelium. And the response of relaxation of rat aorta induced by nitroprusside was not influenced by arsenic stress, but acetylcholine was a little increased. compared to that of control. There were no significant difference in relaxation between control and arsenic treated rings with endothelium or denuded. All of the results, phenyleprine-induced vascular contraction was significantly enhanced in 4 mM arsenic-treated rat aortic rings compared with control, whether endothelium was present or denuded at 8 hours after arsenic treatment. It may be a mechanism by which long-term arsenic stresses play a role in development of hypertension.

Improved preservation of coronary endothelial function with Celsior compared with blood and crystalloid solutions in heart transplantation

Background Endothelial injury from preservation solutions has been implicated in acute coronary vasospasm and pathologic activation of the endothelium, which can contribute to the development of graft coronary vasculopathy after heart transplantation. Preservation solutions with a powerful antioxidant capacity may decrease the occurrence of these complications. Materials and methods This study was designed to evaluate the effect of Celsior (an anti-oxidant solution specifically designed for cardiac preservation) in a model of heart preservation (4 hours at 4° C to reproduce the situation encountered in clinical heart transplantation) compared two commonly used cardioplegic and preservation strategies on coronary endothelial function. Endothelium-dependent relaxation of normal porcine epicardial coronary arteries to serotonin (5-HT, an agonist that activates 5-HT 1d receptors coupled to Gi proteins) and bradykinin (BK, which activates B2 receptors coupled to Gq proteins) was studied in standard organ chamber experiments in the following groups: a control group was submitted to immediate excision without cardioplegia and preserved in saline solution (0.9% NaCl) for 4 hours (Group 1); two groups had cardioplegia induced with a crystalloid solution and were stored for 4 hours in saline (Group 2) or 4 hours in Celsior solution (Group 3); and two groups had cardioplegia induced with normothermic blood cardioplegia and were stored for 4 hours in the saline (Group 4), or 4 hours in Celsior solution (Group 5). Finally, two groups underwent cardioplegia with Celsior and were stored for 4 hours in saline (Group 6), or 4 hours in the Celsior solution (Group 7). All cardioplegia solutions were at 4° C (except blood cardioplegia at 37° C) and all preservations solutions were at 4° C. Results Endothelium-dependent relaxations to serotonin were significantly decreased in all groups except the Celsior + Celsior group compared with the control group. There were no significant differences in relaxation to bradykinin except in one group. Use of the Celsior solution for induction of cardioplegia and storage better preserved endothelium-dependent G-protein–mediated relaxation compared with the other arrest and preservation strategies. Conclusions The observed effect may be associated with an improvement in both short- and long-term outcome in heart transplantation, especially because these alterations may be further compounded by reperfusion.

Effects of doxorubicin on diastolic function, contractile reserve, and ventricular-vascular coupling in piglets.

The use of doxorubicin as an anticancer drug is limited by its cardiac toxicity. To examine the adverse effects of doxorubicin on cardiac function and ventricular-vascular coupling in piglets, eight piglets received five doses of intravenous doxorubicin, 1.5 mg/kg/dose, every 4-7 days starting at 3 weeks of age. A control group consisted of eight normal piglets. Using conductance and manometric catheters, indices of cardiac function, including end systolic elastance (Ees), preload-recruitable stroke work, dP/dtmax, tau, dP/dtmin, dV/dtmax, and end systolic stiffness, were calculated from volume and pressure measurements at rest and during infusion of isoproterenol. Ventricular-vascular coupling was examined by measuring arterial elastance (Ea) and Ea/Ees. Significant differences in relaxation were found between groups. Indices of diastolic stiffness and of contractile function were not different between groups. Baseline contractile efficiency was increased in the doxorubicin group. Ea and Ea/Ees were lower in the doxorubicin group. Ea/Ees was near 1 at baseline in the doxorubicin group, indicating that conditions were optimized for performance of external stroke work. Therefore, the reserve to increase external cardiac work was diminished. The finding of altered diastolic function suggests the importance of screening of diastolic indices to detect the earliest disturbances in cardiac function caused by doxorubicin.

Effects of cardioplegic solutions on the vasoreactivity of the internal mammary artery

Background. During free internal mammary artery grafting, cardioplegia administration can be performed through the internal mammary artery. The present study examined whether cardioplegic solutions produce arterial graft constriction and functional endothelial damage. Methods. Forty internal mammary artery segments from 10 patients were incubated in Krebs solution (n = 10), University of Wisconsin solution (n = 10), Broussais Hospital solution (n = 10), or blood cardioplegia (n = 10). Results. There was a significant difference in sensitivity to norepinephrine between segments in Krebs solution and those in University of Wisconsin solution or Broussais Hospital solution but not segments in blood cardioplegia. There was a significant difference in relaxation to acetylcholine between segments in Krebs solution and those in the three other cardioplegic solutions and between those in blood cardioplegia and segments in University of Wisconsin solution or Broussais Hospital solution. There was no significant difference in relaxation to sodium nitroprusside between segments in any of the solutions. Conclusions. These experiments suggest that storage in the different cardioplegic solutions studied does not preserve the initial vasoreactivity of the internal mammary artery. However, blood cardioplegia appears to be less deleterious in regard to endothelial and myogenic vascular function.

LACK OF INVOLVEMENT OF NITRIC OXIDE IN MEDIATING INCREASED MICROVASCULAR REACTIVITY IN DEOXYCORTICOSTERONE-ACETATE SALT HYPERTENSIVE RATS. • 312

Previous studies in our laboratory have demonstrated that arteriolar dilation mediated by stimulation of endogenous nitric oxide (NO) release, are depressed during the established stage of hypertension in the spontaneously hypertensive rat. In this study, the microvascular reactivity and the effects of NO blockade were examined in two groups of male Sprague-Dawley rats: normotensive control (NT) and deoxycorticosterone-acetate salt (DOCA) hypertensive. Hypertension was induced in the experimental group by twice a week subcutaneous injections of 30mg/kg of the DOCA-salt after uni-nephrectomy. The NT (BP=130±8; n=6) and DOCA (BP=168±1; n=6) groups were maintained on a normal and high sodium and potassium diet, respectively. Third order arterioles responses in the cremasteric muscle were then observed via in vivo closed circuit television microscopy at four weeks after induction of hypertension. Exposure of the microvasculature to acetylcholine or sodium nitroprusside did not reveal any significant differences in relaxation between arterioles of the NT and DOCA groups. In addition, NO blockade with Nw-nitro-L-arginine methyl ester (L-NAME) produced significant reductions in resting arteriolar diameters in both groups that were similar (41±13% and 48±10%, respectively). However, an increase in contractile sensitivity to norepinephrine was observed in the DOCA rats. These data indicate that basal and stimulated release of NO is not attenuated in the late stages of DOCA-salt hypertension. Thus, attenuation of NO release does not to appear to be responsible for the elevated microvascular reactivity associated with DOCA-salt hypertension.

Chronic lead exposure may inhibit endothelium-dependent hyperpolarizing factor in rats.

We designed experiments to determine the effect of chronic lead exposure on endothelium-dependent responses to acetylcholine (Ach) in rat isolated blood vessels. Male Wistar rats were maintained for 1 or 3 months with or without oral lead administration. Membrane potential and isometric tension were measured in mesenteric arteries. Ach caused concentration- and endothelium-dependent relaxation in rings with endothelium contracted with phenylephrine (PE). There was no significant difference in relaxation between lead-exposed and control animals. In the presence of NG-nitro-L-arginine methyl ester (L-NAME), both endothelium-dependent hyperpolarization and relaxation to Ach were significantly reduced in animals from the 3-month lead-exposed group. In aorta from lead-exposed groups, endothelium-dependent relaxation to Ach was not significantly different from that of age-matched controls, whereas both were completely inhibited in the presence of L-NAME. The basal levels of cyclic GMP in the aorta were not affected by lead exposure regardless of duration. These data indicate that both endothelium-dependent hyperpolarization and L-NAME-resistant relaxation decrease with chronic lead exposure in rat mesenteric arteries and suggest that lead is an inhibitor or endothelium-derived hyperpolarizing factor (EDHF).

Antenatal betamethasone therapy augments nitric oxide-mediated relaxation of preterm ovine pulmonary veins.

Antenatal glucocorticoid therapy improves pulmonary function in preterm newborns. We have determined the effect of antenatal glucocorticoid therapy on nitric oxide-mediated relaxation in pulmonary vessels of preterm lambs. Ovine fetuses (126 days gestation; full term = 150 days) were injected with betamethasone (0.5 mg/kg body wt) or saline. After 48 h, lambs were delivered, ventilated for 3 h, and killed. Isolated fourth-generation pulmonary arteries (2-3 mm diameter) and veins (1.5-2 mm diameter) were suspended in organ chambers filled with modified Krebs-Ringer solution (95% O2-5% CO2) at 37 degrees C, and their isometric tension was recorded. During contractions to endothelin-1 or U-46619 (in the presence of indomethacin), acetylcholine and bradykinin induced endothelium-dependent nitro-L-arginine-inhibitable relaxation in arteries and veins. The relaxation was greater in veins of betamethasone-treated than in those of control lambs. Veins from lambs without endothelium treated with betamethasone were more sensitive to sodium nitroprusside than veins from controls. For arteries, there was no significant difference in relaxation between different groups. Relaxation induced by 8-bromoguanosine 3',5'-cyclic monophosphate was similar in arteries and veins of different groups. Radioimmunoassay showed that nitric oxide caused a greater increase in guanosine 3',5'-cyclic monophosphate in betamethasone-treated veins than in controls. These data suggest that antenatal betamethasone therapy augments nitric oxide-mediated relaxation of pulmonary veins of preterm lambs, probably by increasing soluble guanylate cyclase activity of vascular smooth muscle.

Vasodilatory responses of isolated arteries of cirrhotic rats.

1. There is currently considerable interest in the role of locally produced vasodilators such as nitric oxide and adenosine in the pathogenesis of the peripheral vasodilatation of cirrhosis. However, the signal transduction pathways involving guanylate cyclase and adenylate cyclase have not been clearly delineated in the isolated blood vessel. 2. We therefore aimed to examine the in vitro vasorelaxant effects of the endothelium-dependent dilator bethanechol, the endothelium-independent dilator sodium nitroprusside and adenosine, as drugs that work via activation of guanylate and adenylate cyclases, in isolated aortic and superior mesenteric arterial rings from cirrhotic and control rats. 3. Cirrhosis was induced by chronic bile duct ligation and section of 24-28 days' duration, while controls underwent sham operation. The vessels were precontracted with the alpha 1-adrenoceptor agonist phenylephrine, then relaxed by incremental doses of the three drugs. 4. Marked attenuation of vasoconstriction induced by phenylephrine in isolated aortic and mesenteric arterial rings from cirrhotic rats compared with the control vessels was observed. 5. There were no significant differences in relaxation between the cirrhotic and control vessels to the three drugs. We conclude that in vitro vasodilatory responses mediated through signal transduction pathways involving guanylate cyclase and adenylate cyclase remain unchanged in a rat model of biliary cirrhosis.

Diabetes Mellitus Impairs Neurogenic and Endothelium-Dependent Relaxation of Rabbit Corpus Cavernosum Smooth Muscle

The effect of alloxan-induced diabetes on the reactivity of corporeal nerves, endothelium and smooth muscle was studied in the New Zealand white rabbit. Fifteen rabbits were randomly divided into treated (n = 6) and control (n = 9) groups. The treated group was maintained for 6 weeks. Two control groups were studied. One control group (n = 3) was maintained for 6 weeks as littermate controls for diabetic group. The second control group (n = 6) was not maintained but was weight matched with the 6 week diabetic group. The reactivity of corpus cavernosum tissue from the diabetic animals and the control animals was studied in organ chambers. When tissue contraction was produced with phenylephrine for the study of relaxation to various stimuli, the tension induced was similar in the diabetic and the control groups. Relaxation of corpus cavernosum tissue to electrical stimulation of autonomic nerves as well as relaxation to the endothelium-dependent vasodilator acetylcholine were comparably unaffected in the weight matched and littermate control groups while significantly inhibited in the diabetic group. Treatment of the corporeal tissue with the cyclooxygenase inhibitor indomethacin enhanced the relaxation to electrical stimulation and to acetylcholine in the control and in the diabetic groups but did not improve the significant difference in relaxation between the two groups. Relaxation of corporeal tissue to endothelium-independent vasodilators, papaverine and nitroprusside was similar in the control groups and the diabetic groups. It is concluded that diabetes impairs neurogenic and endothelium-mediated relaxation of rabbit corpus cavernosum smooth muscle. These findings are comparable to those described in corpus cavernosum tissue from diabetic men, showing the validity of this experimental animal model. The mechanism for the nerve or endothelial dysfunction does not appear to involve alteration in cyclooxygenase products of arachidonate or the ability of the corporeal smooth muscle to relax via a cGMP-dependent mechanism. Since nitric oxide has been shown to act as the nonadrenergic noncholinergic neurotransmitter as well as endothelium-derived relaxing factor (EDRF) of the trabecular smooth muscle, it is possible that impairment of neurogenic and endothelium-dependent relaxation due to diabetes is mediated by alteration in the synthesis or availability of nitric oxide in corporeal tissue.

Effects of DNA gyrase inhibitors in Escherichia coli topoisomerase I mutants.

Relaxation of titratable supercoils in bacterial nucleoids was measured following treatment of topA mutants with coumermycin or oxolinic acid, inhibitors of DNA gyrase. Relaxation occurred after treatment of the mutants with either inhibitor. We detected no significant difference in relaxation between topA- and topA+ strains treated with coumermycin. This finding, together with previous observations, supports the idea that relaxation caused by coumermycin probably arises from the relaxing activity of gyrase itself. The source of DNA relaxation caused by oxolinic acid was not identified. Nucleoid supercoiling can be increased by adding oxolinic acid to a strain that carries three topoisomerase mutations: delta topA, gyrB225, and gyrA (Nalr) (S. H. Manes, G. J. Pruss, and K. Drlica, J. Bacteriol. 155:420-423, 1983). We found that this increase in supercoiling requires partial sensitivity to the drug and at the delta topA and gyrA mutations. Full resistance to oxolinic acid in the presence of the delta topA, gyrB225, and gyrA mutations was conferred by an additional mutation that maps at or near gyrB.