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At least 19 recordsLinked to original sources
PubMed1990

Assessment of left ventricular relaxation by Doppler echocardiography. Comparison of isovolumic relaxation time and transmitral flow velocities with time constant of isovolumic relaxation.

Isovolumic relaxation time (IVRT) and events of early transmitral flow measured by Doppler echocardiography were validated against the time constant of left ventricular relaxation (tau) in open-chest dogs. During increased inotropy (by isoproterenol infusion) at constant preload, enhancement of relaxation was indicated by a decrease in tau from 48 +/- 12 (mean +/- SD) to 33 +/- 5 msec (p = 0.04) with a concomitant decrease in IVRT from 74 +/- 18 to 38 +/- 8 msec (p = 0.03). During decreased inotropy (by propranolol infusion) at constant preload, slowing of relaxation was indicated by an increase in tau from 40 +/- 8 to 51 +/- 13 msec (p = 0.02) with a concomitant increase in IVRT from 71 +/- 15 to 83 +/- 21 msec (p less than 0.05). A significant correlation between changes in tau and changes in IVRT was found (r = 0.66, p less than 0.001). In contrast, when left ventricular end-diastolic pressure was increased from 7 +/- 2 to 24 +/- 4 mm Hg at constant inotropy, tau increased from 47 +/- 14 to 64 +/- 25 msec (p = 0.03), whereas no change in IVRT was observed (76 +/- 19 and 71 +/- 19 msec, respectively). Aortic pressure was not significantly changed during any intervention, and heart rate was kept constant by pacing. Peak early transmitral velocity was unchanged by propranolol but increased during isoproterenol and saline infusion (p less than 0.001 and p less than 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Phosphodiesterase inhibitors induce endothelium-dependent relaxation of rat and rabbit aorta by potentiating the effects of spontaneously released endothelium-derived relaxing factor.

The selective cyclic GMP phosphodiesterase inhibitor M&B 22948 and the less selective phosphodiesterase inhibitors papaverine and isobutylmethylxanthine (IBMX) each induced a component of relaxation of rat aortic rings that was endothelium-dependent. The most selective agent at inducing endothelium-dependent relaxation was M&B 22948, which caused little relaxation of endothelium-denuded rings at concentrations that produced almost complete relaxation of endothelium-containing rings. Although endothelium-dependent components of relaxation induced by papaverine and IBMX were clearly present, they were less well separated from the endothelium-independent components of relaxation. In the aorta of the rabbit, M&B 22948 and papaverine were less affective at inducing an endothelium-dependent component of relaxation than in the aorta of the rat, and IBMX produced no discernible endothelium-dependent component. The endothelium-dependent components of relaxation induced by M&B 22948, papaverine and IBMX on rat and rabbit aorta were probably dependent on endothelium-derived relaxing factor (EDRF), because they were associated with concomitant endothelium-dependent rises in cyclic GMP, and these components of relaxation as well as the rises in cyclic GMP were completely blocked by the EDRF-blocking agent hemoglobin. The action of hemoglobin was entirely specific, as none of the endothelium-independent components of relaxation induced by any of the phosphodiesterase inhibitors was affected by this hemoprotein. It is likely that the phosphodiesterase inhibitors induce their endothelium-dependent components of relaxation by inhibiting the hydrolysis of cyclic GMP formed in response to EDRF released spontaneously from endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1975

Relaxation complexes of poasmid DNA and protein. III. Association of protein with the 5' terminus of the broken DNA strand in the relaxed complex of plasmid ColE1.

The location of the protein in the open circular DNA form of the ColE1 DNA-protein relaxation complex, induced by treatment with sodium dodecyl sulfate, has been studied using several enzymes of DNA metabolism. Escherichia coli exonucleases I and III are able to degrade extensively the nicked strand of the relaxed complex from the 3' end. DNA polymerase I can initiate synthesis using the relaxed complex as template-primer and specifically extends the 3' end of the nicked strand. The 5' end of the sodium dodecyl sulfate-relaxed complex, however, is blocked to the 5'-3' hydrolitic action T7 exonuclease. This block remains after trypsin treatment of the sodium dodecyl sulfate-relaxed complex but is removed by Pronase treatment. T4 DNA ligase is unable to seal either the sodium dodecyl sulfate-relaxed complex or the Pronase-treated relaxed complex even after pretreatment of the relaxed complex with T4 DNA polymerase and polynucleotide kinase. However, pretreatment with DNA polymerase I and the four deoxyribonucleoside triphosphates facilitates ligase closure of the Pronase-treated relaxed complex but not the sodium dodecyl sulfate-relaxed complex. These studies indicate that the protein in the relaxed ColE1 complex is located at or near the 5' end of the nicked strand.

Bacterial Proteins↗
PubMed1992

Characterization of the receptor mediating relaxation to substance P in canine middle cerebral artery: no evidence for involvement of substance P in neurogenically mediated relaxation.

1. The aim of this study was to characterize the neurokinin receptor which mediates relaxation of dog isolated middle cerebral artery by the use of selective agonists and antagonists and to establish whether substance P is involved in the neurogenically mediated relaxant response in this vessel. 2. Substance P caused concentration-related, endothelium-dependent relaxations of dog isolated middle cerebral artery, contracted with prostaglandin F2 alpha. The selective NK1 receptor agonists, GR73632 and substance P methyl ester (SPOMe), also caused relaxation with similar maximum effects to those of substance P. GR73632 and SPOMe were approximately 20 times and 6 times less potent respectively than substance P. The selective NK2 and NK3 receptor agonists, GR64349 and senktide, were only weakly active in causing relaxation being at least 425 times and 245 times less potent respectively than substance P. 3. The selective NK1 receptor antagonist, GR82334, was a potent, specific, competitive antagonist of the relaxant effects of substance P. In contrast, the selective NK2 receptor antagonist, R396 (10 microM) had no effect on the response to substance P. 4. Electrical field stimulation of dog isolated middle cerebral artery, contracted with prostaglandin F2 alpha, caused neurogenically mediated, non-adrenergic non-cholinergic (NANC) relaxations. These NANC relaxations were unaffected by endothelium removal, GR82334 (10 microM) or by capsaicin (10 microM) treatment. However, the nitric oxide synthesis inhibitor, L-NG-monomethyl arginine methyl ester (L-NMMA) (100 microM) markedly attenuated the response to electrical stimulation. 5. These results suggest that substance P causes relaxation of dog isolated middle cerebral artery via activation of NK1 receptors. However, substance P does not appear to be involved in NANC neurotransmission. In contrast, the marked inhibitory effect of L-NMMA on NANC relaxations implicates nitric oxide in NANC neurotransmission in this vessel.

Animals↗
PubMed1990

Comparison of relaxation responses of vascular and non-vascular smooth muscle to endothelium-derived relaxing factor (EDRF), acidified sodium nitrite (NO) and sodium nitroprusside.

Smooth muscle relaxant activity of endothelium-derived relaxing factor (EDRF) released from columns of cultured bovine endothelial cells by bradykinin (0.1-3 nmol/l) was measured in four non-vascular preparations: guinea-pig taenia caeci, guinea-pig trachea, rat stomach (fundus) and rat anococcygeus. Each preparation was contracted to a steady level of force with a variety of agonists such that they relaxed optimally to sodium nitroprusside (SNP). The EDRF-induced relaxations in each preparation were compared with those obtained in de-endothelialized ring preparations of greyhound coronary artery by means of paired bioassays run in parallel. EDRF released from the endothelial cell columns caused 80-100% relaxation of the coronary artery, 40-80% in the guinea-pig taenia caeci, 50-70% in the rat anococcygeus, 5-8% in the guinea-pig trachea and was undetectable in the rat stomach strip. By comparison, SNP caused maximal relaxation in all tissues compared with the coronary artery. In separate organ bath experiments the sensitivity to nitric oxide (NO: generated by adding acidified solutions of NaNO2) and SNP was compared in each preparation. SNP caused maximal relaxation in all tissues with the following order of potency: dog coronary artery greater than guinea-pig trachea greater than guinea-pig taenia = rat anococcygeus greater than rat stomach strip. In contrast, the concentration of acidified NaNO2 (NO, 300 nmol/l) that caused 96 +/- 4% relaxation in the dog coronary artery caused 84 +/- 7% and 48 +/- 1% relaxation in the taenia and anococcygeus respectively. No response attributable to NO was detected in either the trachea or rat stomach strip.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

Asynchronous ventricular relaxation: an angiographic temporal analysis of asynchronous left ventricular relaxation in man.

Segmental "early relaxation" is a common angiographic finding. An attempt was made to elucidate the temporal characteristics of this event. Twenty subjects with and 20 without segmental early relaxation were studied. The left ventricular diastolic relaxation time was precisely determined angiographically, and the findings were as follows: 0.12 +/- 0.04 second (mean +/- standard deviation) in the normal patients, 0.14 +/- 0.03 second in the patients with coronary artery disease but no segmental early relaxation and 0.20 +/- 0.04 second in the patients with segmental early relaxation. These findings indicate that early relaxation is associated with a significantly prolonged ventricular relaxation time. The use of the term asynchronous ventricular relaxation is proposed to denote the disturbed diastolic properties of the ventricle with "early relaxation."

Angiocardiography↗
PubMed1976

Protein rotational relaxation as studied by solvent 1H and 2H magnetic relaxation.

Earlier studies of the magnetic field dependence of the nuclear spin magnetic relaxation rate of solvent protons in solutions of diamagnetic proteins have indicated that this dependence (called relaxation dispersion) is related to the rotational Brownian motion of solute proteins. In essence, the dispersion is such that 1/T1 (the proton spin-lattice relaxation rate) decreases monotonically as the magnetic field is increased from a very low value (approximately 10 Oe); the dispersion has a point of inflection at a value of magnetic field which depends on protein size, shape, concentration, temperature, and solvent composition. The value of the proton Larmor precession frequency nu(c) at the inflection field appears to relate to tau (R), the rotational relaxation time of the protein molecules. We have measured proton relaxation dispersions for solutions of various proteins that span a three-decade range of molecular weights, and for one sample of transfer ribonucleic acid. We have also measured deuteron relaxation dispersions for solutions of three proteins: lysozyme, carbonmonoxyhemoglobin, and Helix pomatia hemocyanin with molecular weight 900 000. A quantitative relationship between both proton and deuteron dispersion data and protein rotational relaxation is confirmed, and the point is made that magnetic dispersion measurements are of very general applicability for measuring the rotational relaxation rate of macromolecules in solution. It has been previously shown that the influence of proton motion on the relaxation behavior of the solvent is not due to exchange of solvent molecules between the bulk solvent and a hydration region of the protein. In the present paper, we suggest that the interaction results from a long range hydrodynamic effect fundamental to the situation of large Brownian particles in an essentially continuum fluid. The general features of the proposed mechanism are indicated, but no theoretical computations are presented.

Deuterium↗
PubMed1992

Relationship between chronic hypoxia and in vitro pulmonary relaxation mediated by endothelium-derived relaxing factors in human chronic obstructive lung disease.

Endothelium-derived relaxing factors (EDRF) are paracrine vasodilator substances released by endothelial cells. There is compelling evidence to suggest that EDRF may play an important role in the modulation of vascular tone in the systemic circulation. However, the role of EDRF-mediated pulmonary relaxation in chronic lung disease is unknown. The authors have, therefore, investigated endothelium-dependent relaxation of isolated pulmonary arteries (PAs) obtained from 18 patients undergoing heart-lung transplantation for end-stage chronic hypoxic cor pulmonale (HCP). Control PAs were obtained from 10 patients, none of whom had evidence of HCP, and who underwent lobectomy for lung carcinoma. All vascular rings were studied immediately after lung excision. PA rings from control patients dose-dependently relaxed to cumulative doses of acetylcholine (ACh, 10(-10) to 10(-5) M), achieving a maximal relaxation of 73.2 +/- 4.4% from precontraction to phenylephrine. By contrast, PA rings from HCP patients achieved only 42.1 +/- 6.7% of maximal relaxation (p less than 0.01). Sodium nitroprusside (10(-4) M) relaxed all PA rings, with and without endothelium (carefully removed before study), obtained from both control and HCP patients. The endothelium-dependent maximal relaxation to ACh was positively related to pretransplant values of PaO2 (r = 0.59; p less than 0.01), but no relationship was found with either PaCO2 (r = -0.41) or FEV1 (r = -0.14). The authors conclude that pulmonary relaxation mediated by EDRF is impaired in human HCP and suggest that such impairment may be related to severity of the preexisting chronic hypoxemia.

Acetylcholine↗
PubMed1992

Isometric squeeze relaxation (progressive relaxation) vs meditation: absorption and focusing as predictors of state effects.

We taught isometric squeeze relaxation (a variant of progressive relaxation) or meditation to 52 anxious subjects (16 men, 36 women). For meditation, pretreatment high absorption correlated with reductions in state cognitive and somatic anxiety as well as increments in state focusing. For isometric squeeze relaxation, pretreatment low state focusing correlated with reductions in somatic anxiety and increments in focusing. Results suggest that isometric squeeze relaxation (and progressive relaxation) may be more appropriate for individuals who have difficulty focusing, and meditation for those who already possess well-developed relaxation skills at a trait level. The results appear more consistent with Smith's cognitive-behavioral model of relaxation than with Benson's relaxation response or Davidson and Schwartz's specific effects models.

Adult↗
PubMed1992

Highly potent beta-2 sympathomimetics convert to less potent partial agonists as relaxants of guinea pig tracheae maximally contracted by carbachol. Comparison of relaxation with receptor binding and adenylate cyclase stimulation.

Beta-adrenergic agonists are among to the most potent dilators of airway smooth muscle available and act as functional antagonists of a variety of contractile stimuli. In order to elucidate their loss of relaxant potency in dependence on antagonistic stimuli tracheal relaxation by the beta-2 sympathomimetics (+/-)-salbutamol (+/-)-fenoterol, and (+/-)-formoterol was compared to (-)-isoprenaline in guinea pig tracheae partially and maximally precontracted by carbachol. In partially precontracted tracheae, salbutamol, fenoterol and formoterol exerted maximum relaxation with low EC50 of 20, 5.6 and 0.29 nmol/l, respectively. In maximally precontracted tracheae, however, salbutamol, fenoterol and formoterol were only partial agonists for relaxation with different intrinsic activities (0.62, 0.62 and 0.77, respectively) and increased EC50 (120, 50 and 3.6 nmol/l, respectively). A reduction of relaxant potency by increased muscarinic stimuli was also observed for beta-1 adrenoceptors stimulated by (-)-noradrenaline after blockade of beta-2 adrenoceptors. In order to investigate if the reduced relaxant potency of beta-2 sympathomimetics was caused by a reduced spare receptor capacity or a reduced intrinsic activity for stimulation of adenylate cyclase (AC), we performed experiments in membranes from lung and tracheal cells. In radioligand binding, beta-2 sympathomimetics recognized the high-affinity state (57%) of the beta-2 adrenoceptor with a lower effectiveness than (-)-isoprenaline, which exhibited a 100-fold higher affinity for high over low-affinity states. Dissociation constants for the low-affinity state matched EC50 for AC stimulation. Intrinsic activities (%) for AC stimulation were significantly lower for salbutamol (67%), fenoterol (67%) and formoterol (89%) than for (-)-isoprenaline (100%), indicating that the reduced relaxation potency of the beta-2 sympathomimetics of maximally precontracted tracheae is caused by a reduced intrinsic activity for AC stimulation. It might be speculated that formoterol could improve drug therapy of asthma due to its high binding affinity and its high intrinsic activity for relaxation.

Adenylyl Cyclases↗
PubMed1992

Formoterol, fenoterol, and salbutamol as partial agonists for relaxation of maximally contracted guinea pig tracheae: comparison of relaxation with receptor binding.

In severe asthma attacks beta 2-sympathomimetics lose part of their therapeutic efficiency. To elucidate this loss of efficiency in an experimental model we compared the relaxant potency of salbutamol (SAL), fenoterol (FEN), formoterol (FOR), and (-)-isoprenaline (ISO) in guinea pig tracheae partially and maximally precontracted by 0.1 and 60 mumol/L carbachol, respectively. In partially precontracted tracheae the beta 2-sympathomimetics exerted maximum relaxation in comparison with ISO and low EC50S (nmol/L) for relaxation (SAL, 20; FEN, 5.6; FOR, 0.28; and ISO, 2.5). In maximally precontracted tracheae, however, the beta 2-sympathomimetics were only partial agonists for relaxation with reduced intrinsic activities (%) in comparison to ISO (SAL, 59%; FEN, 61%; FOR, 76%) and significantly increased EC50S (nmol/L) for relaxation (SAL, 130; FEN, 57; FOR, 3.0; ISO, 37). To investigate if the high relaxant potency of FOR is correlated with a higher binding affinity and/or a higher intrinsic activity for adenylate cyclase stimulation than for FEN and SAL, we performed experiments in receptor membranes from guinea pig lung. Binding competition of SAL, FEN, and FOR with [3H]ICI 118,551 for lung beta 2-adrenoceptors yielded dissociation constants (KD) of 320 (SAL), 120 (FEN), and 7.6 (FOR) nmol/L, which exhibited the same ranking as EC50S for relaxation. Concentrations of SAL, FEN, and FOR equivalent to 100 KD of the respective dissociation constants stimulated beta 2-adrenoceptor-coupled adenylate cyclase with different intrinsic activities (%) incomparison to ISO (SAL, 61%; FEN, 63%; FOR, 89%) matching intrinsic activities for relaxation. From these experiments it may be concluded that FOR might improve drug therapy of severe asthma not only due to its long mode of action discovered in clinical studies but also due to its high intrinsic activity and receptor affinity.

Adenylyl Cyclases↗
PubMed1990

Quantitative studies of hydrodynamic effects and cross-relaxation in protein solutions and tissues with proton and deuteron longitudinal relaxation times.

Longitudinal relaxation times T1 of water protons were measured in 5% protein solutions at different static magnetic fields (0.47, 2, and 7 T), for proteins with molecular weight ranging between 1.4 and 480 kDa and in solvents of varying degrees of deuteration. T1 values were also obtained for rat liver soaked with Krebs-Ringer solutions of varying degrees of deuteration at the above fields. For the samples containing D2O, T1 for deuterium was also measured at fields 2 and 7 T. The deuterium measurements were used to estimate water rotational correlation times which were in turn used to estimate the contribution of so-called "hydrodynamic effects" of macromolecules to proton relaxation. The proton relaxation rates at full deuteration were compared with those in protonated solvent (water) to obtain a second, direct measurement of this effect. Both measurements provide quantitation of the hydrodynamic effects, free from the contributions of other effects that are transparent to deuteration, and results from both measurements agree with each other reasonably well. The cross-relaxation rate between solute and solvent protons, and the contribution of paramagnetic impurities in the samples were also obtained from the proton T1 studies. The experimental results show that the hydrodynamic effects (intramolecular and intermolecular water-water interactions) are about the same magnitude in all the proteins studied as well as in rat liver. However, the cross-relaxation rate generally increases with increasing protein molecular weight. Measurements in soaked rat liver indicate that the cross-relaxation rate per unit mass of solute is much higher in tissues than in simple solutions of proteins of similar mean molecular weight. The results challenge the prevailing concept that the relaxation properties of biological tissues may be treated as a simple superposition of the properties of their constituents.

Animals↗
PubMed1992

Bradykinin-induced, N omega-nitro-L-arginine-insensitive endothelium-dependent relaxation of porcine coronary arteries is not mediated by bioassayable relaxing substances.

The effect of the arginine analogue, N omega-nitro-L-arginine (L-NNA) was studied on bradykinin-induced relaxation in porcine coronary arteries. In the presence of indomethacin (3 x 10(-6) M) and captopril (10(-6) M), treatment with L-NNA (10(-4) M) had no effect on the bradykinin-induced (10(-10)-10(-7) M) relaxations in strips contracted with U-46619. In contrast to the findings in organ chamber experiments, bradykinin-induced release of endothelium-derived relaxing factor(s) (EDRFs) was abolished after 45 min of treatment of perfused porcine coronary artery segments with L-NNA (10(-4) M) in a superfusion bioassay system. These results show that, in addition to the release of nitric oxide, endothelium-dependent relaxation of porcine coronary arteries to bradykinin involves an alternative mechanism(s), which accounts for the relaxation in the presence of L-NNA. Since the release of a relaxing mediator could not be detected from L-NNA-treated porcine coronary artery segments under bioassay conditions, it is postulated that either no diffusible factor(s) is involved in the L-NNA-insensitive endothelium-dependent relaxation, or it is mediated by an extremely labile endothelium-derived substance(s).

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1987

Selective inhibition by gossypol of endothelium-dependent relaxations augments relaxations to glyceryl trinitrate in rabbit coeliac artery.

1 Acetylcholine, substance P, prostaglandin E1 and the nitrovasodilator glyceryl trinitrate induced concentration-dependent relaxations of endothelium-intact strips of rabbit coeliac artery precontracted with noradrenaline. 2 Endothelium-denuded strip preparations contracted to acetylcholine and showed no response to substance P. The relaxant response to prostaglandin E1 was unimpaired after removal of endothelium, whereas the response to glyceryl trinitrate was increased. 3 A 20 min exposure of endothelium-intact strips to gossypol, an irreversible inhibitor of the production and/or release of endothelium-derived relaxing factor, abolished vasodilatation in response to the endothelium-dependent agents acetylcholine and substance P, did not change relaxations to prostaglandin E1, but significantly enhanced relaxations in response to glyceryl trinitrate. 4 In view of the assumed common mechanism of action of endothelium-derived relaxing factor and nitrovasodilators, these results suggest an interference of the two active principles at the level of the vascular smooth muscle cell.

Acetylcholine↗
PubMed1990

Recurrent tension headache in adolescents treated with self-help relaxation training and a muscle relaxant drug.

Forty-eight adolescents suffering from recurrent tension headache participated in a controlled trial conducted in a high school setting. During the first treatment phase self-help relaxation training was compared with a waiting-list group. Following this phase a pharmacological regimen consisting of a muscle relaxant (chlormezanone) and placebo was superimposed on relaxation therapy in a double-blind crossover design. Each treatment phase encompassed a 5-week period. In addition to the evaluation of headache complaints, psychological distress among students was measured with respect to their experience of somatic complaints, depressive, anxiety and stress symptoms. Although self-help relaxation training significantly decreased the severity and annoyance of adolescents' headache besides their somatic complaints, the clinical improvement of headache was modest. The addition of chlormezanone did not help those who were nonresponders to self-help relaxation training. Finally, a set of pretreatment variables consisting of baseline headache severity and annoyance, experience of anxiety and daily life stress among adolescents could predict outcome of self-help relaxation therapy.

Adolescent↗
PubMed1989

1H magnetic resonance of human tumours. Analysis of the transverse relaxation of the methylene protons using continuous distributions of relaxation times.

In tumours, the decay of 1H transverse magnetization (relaxation profile) of the methylene resonances is usually not a single exponential. The conventional sum-of-exponentials approximation often leads to several solutions which fit the experimental data; choosing one solution over another is highly subjective. We have therefore analyzed transverse relaxation data for the methylene resonance of lipids in human tumours, assuming a continuous distribution of relaxation times. We have studied 89 colon tumours (27 with metastasis), 12 'normal' colon tissues, 40 breast tumours (24 with metastasis) and 13 malignant lymph nodes. All were primary tumours and the patients had received no previous treatment. Two continuous distribution approximations were tested. The two-parameter lognormal distribution provides a simple representation of the relaxation profile. The constrained regularization method (Contin) complements and extends the lognormal approach. The average T2 values, mean value of T2, whether derived from the lognormal or the Contin approximations, are consistent and comparable. Tumour and 'normal' colon tissue taken from the same patient show important differences in relaxation behaviour. A considerable broadening of the lognormal distribution, with mean value of T2 shifted to shorter values, is observed for the colon tumours. This is verified by the constrained regularization method. The 'normal' colon tissues are usually characterized by a single, relatively narrow distribution, while tumours show one or more broad peaks. A substantial broadening of the distribution of relaxation times is observed in colon tumours, whether metastasized or not. A similar broadening is noted for breast tumours and malignant lymph nodes, although the range is slightly less than for colon tumours.(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1992

Potentiation of endothelium-dependent relaxations to bradykinin by angiotensin I converting enzyme inhibitors in canine coronary artery involves both endothelium-derived relaxing and hyperpolarizing factors.

Studies were designed to investigate the mechanisms underlying the augmentation by angiotensin I converting enzyme (ACE) inhibitors of the endothelium-dependent relaxations evoked by bradykinin. Isometric tension, tissue levels of cGMP, and transmembrane potential were measured in isolated canine coronary arteries as indications of the respective contribution of nitric oxide and endothelium-derived hyperpolarizing factor. In rings of coronary artery with endothelium, relaxations to bradykinin were potentiated by the ACE inhibitors cilazaprilat and perindoprilat. NG-Nitro-L-arginine (NLA), a nitric oxide synthase inhibitor, impaired relaxations to bradykinin. But the presence of ACE inhibitors partially restored this activity. Bradykinin stimulated the production of cGMP, and this was enhanced significantly by ACE inhibitors, indicating an augmented release of nitric oxide. NLA abolished the increase induced by bradykinin irrespective of the presence of ACE inhibitors. Electrophysiological studies revealed that bradykinin elicited an endothelium-dependent hyperpolarization of vascular smooth muscle that was insensitive to NLA and potentiated by ACE inhibitors. The bradykinin-induced hyperpolarization and NLA-resistant relaxations were transient and impaired by potassium depolarization. Thus, production of endothelium-derived hyperpolarizing factor may account for the NLA-resistant relaxations of canine coronary arteries. The relaxations induced by bradykinin were unaffected by the B1 kinin receptor antagonist des-Arg9,[Leu8]-bradykinin either in the absence or in the presence of NLA but were antagonized by the B2 kinin receptor antagonist D-Arg[Hyp3,D-Phe7]-bradykinin. Molecular exclusion chromatography of 125I-labeled [Tyr8]-bradykinin and its degradation products demonstrated that the breakdown of the kinin by isolated coronary arteries was prevented in the presence of perindoprilat.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin I↗