Coronary Vasodilator Effects Research Articles

Nitrates administered by spray versus tablet: comparison of coronary vasodilation on CT angiography

To compare the coronary vasodilation effects of spray with those induced by tablet administration in coronary CT angiography (CCTA). A total of 2024 patients who underwent CCTA were identified for this retrospective study, including 828 patients with spray (spray group) and 1169 with tablets (tablet group). Of these, 93 patients underwent CCTA at least twice using both spray and tablets. The number of measurable segments and diameters of all 18 segments was measured. The number of measurable segments was compared between groups. No statistically significant differences were evident between these two groups in terms of clinical characteristics. All coronary segments except the ramus intermedius (RI) and left posterior descending artery (L-PDA) were significantly larger in the spray group than in the tablet group (all p< 0.001). In peripheral and branch vessels, as well as in central and main coronary arteries, the diameters were significantly larger in the spray group than in the tablet group (all p< 0.001). Although not always statistically significant, all coronary segments tended to be more measurable on CCTA with spray than with tablet. In the subgroup that underwent CCTA twice using both spray and tablets, all coronary segments except the RI, obtuse marginal artery 2 (OM2), and L-PDA were significantly larger in the spray group than in the tablet group (all p< 0.05). Lingual isosorbide dinitrate (ISDN) spray was more efficacious than sublingual nitroglycerin (NTG) tablets in coronary vasodilation for CCTA. Therefore, lingual ISDN spray should be preferred over sublingual NTG tablets for CCTA. • Lingual ISDN spray was more efficacious than sublingual NTG tablet for coronary vasodilation in coronary CT angiography, even in elderly patients. • The diameters of all coronary segments except RI and L-PDA were significantly larger, and there were significantly more coronary segments greater than 1.5mm, except RI and L-PDA, in the spray group than in the tablet group in the whole study group. • Even in peripheral and branch vessels, the diameters of coronary arteries were significantly larger in the spray group than in the tablet group, and they were also larger in elderly patients.

Blood pressure-lowering effects of a Bowman-Birk inhibitor and its derived peptides in normotensive and hypertensive rats

Bioactive plant peptides have received considerable interest as potential antihypertensive agents with potentially fewer side effects than antihypertensive drugs. Here, the blood pressure-lowering effects of the Bowman-Birk protease inhibitor, BTCI, and its derived peptides, PepChy and PepTry, were investigated using normotensive (Wistar-WR) and spontaneously hypertensive rats (SHR). BTCI inhibited the proteases trypsin and chymotrypsin, respectively, at 6 µM and 40 µM, a 10-fold greater inhibition than observed with PepTry (60 µM) and PepChy (400 µM). These molecules also inhibited angiotensin converting enzyme (ACE) with IC50 values of 54.6 ± 2.9; 24.7 ± 1.1; and 24.4 ± 1.1 µM, respectively, occluding its catalytic site, as indicated by molecular docking simulation, mainly for PepChy and PepTry. Gavage administration of BTCI and the peptides promoted a decrease of systolic and diastolic blood pressure and an increase of renal and aortic vascular conductance. These effects were more expressive in SHR than in WR. Additionally, BTCI, PepChy and PepTry promoted coronary vasodilation and negative inotropic effects in isolated perfused hearts. The nitric oxide synthase inhibitor blunted the BTCI and PepChy, with no cardiac effects on PepTry. The findings of this study indicate a therapeutic potential of BTCI and its related peptides in the treatment of hypertension.

Cardiovascular effects of DWORF (dwarf open reading frame) peptide in normal and ischaemia/reperfused isolated rat hearts

The novel peptide dwarf open reading frame (DWORF), highly conserved across species and expressed almost exclusively in cardiac ventricular muscle, may play a role in cardiac physiology and pathophysiology. The effect of direct administration of DWORF in the intact heart has not previously been examined. Accordingly, we investigated the cardiac effects of DWORF (1−30 nM) in normal isolated perfused rat hearts and hearts undergoing ischaemia/reperfusion (I/R) injury, and evaluated potential mechanisms of action. Exogenous DWORF at the top dose (30 nM) increased perfusion pressure (PP) in normal hearts, which indicates coronary vasoconstriction; and during post-ischaemic reperfusion, DWORF increased PP in a dose-dependent manner. In I/R hearts, DWORF at the top dose also increased left ventricular end-diastolic pressure and maximum and minimum derivatives of left ventricular pressure noted dP/dt(max) and dP/dt(min), respectively, without affecting developed pressure (DP). Co-infusion of DWORF with Diltiazem, an l-type Ca2+ channel blocker (1μM), in I/R hearts attenuated the falls in DP, dP/dt(max) and dP/dt(min) observed with Diltiazem alone. DWORF co-infusion with both Diltiazem and Y27632 (1μM) (a Rho-Kinase inhibitor) reversed the coronary vasodilator effect of the inhibitors administered alone. In conclusion, we provide the first evidence that DWORF has coronary vasoconstrictor actions in normal hearts and when administered during reperfusion in an ex-vivo model of cardiac I/R injury, and also exhibits positive cardiac inotropic activity in the latter setting. DWORF’s effect on ventricular contractile function appears to be dependent on the l-type Ca2+ channel, whereas Rho-Kinase activity may be related to the coronary vasoconstrictor effects of DWORF.

BJ-PRO-7A and BJ-PRO-10C induce vasodilatation and inotropic effects in normotensive and hypertensive rats: Role of nitric oxide and muscarinic receptors

Bj-PRO-7a and Bj-PRO-10c belong to a family of proline-rich oligopeptides (PROs) identified in Bothrops jararaca (Bj) crude venom. Previous studies have shown an antihypertensive effect evoked by theses peptides. However, the mechanisms underlying the direct effects on vessels and heart remain to be unraveled. Thus, we investigated the effect of the Bj-PRO-7a and Bj-PRO-10c in the aorta and coronary arteries and in cardiac contractility in normotensive (Wistar) and hypertensive (SHR) rats. Pre-constricted aortic rings were exposed to increasing concentrations of Bj-PROs in presence or absence of muscarinic type 1 receptor antagonist (Pirenzepine), nonselective muscarinic receptor antagonist (Atropine), nitric oxide synthase inhibitor (L-NAME), guanylyl cyclase inhibitor (ODQ), adenylyl cyclase inhibitor (MDL), or argininosuccinate synthetase inhibitor (MDLA). The effects of Bj-PROs in the cardiac contractility and coronary vasomotricity were evaluated using Langendorff perfused heart preparation. The rat hearts were perfused with Bj-PRO-7a or Bj-PRO-10c in absence or presence of L-NAME, ODQ or MDL. Both Bj-PROs induced endothelium-dependent vasorelaxation in aortic rings from Wistars and SHRs. These effects were inhibited by L-NAME, ODQ or MDL. Atropine and Pirenzepine blocked the vasorelaxant effect of Bj-PRO-7a in aorta from both strains. MDLA inhibited the Bj-PRO-10c-induced vasorelaxation in aortic rings from SHR, but not Wistar. The Bj-PRO-7a induced coronary vasodilation only in SHR. L-NAME, ODQ and MDL inhibited this effect. Bj-PRO-10c induced coronary vasodilatation in both strains, which was blocked by L-NAME, ODQ and MDL. Bj-PRO-7a decreased the dP/dt max in Wistar hearts and the dP/dt min in Wistar and SHR hearts. These effects were abolished by L-NAME. Bj-PRO-10c decreased dP/dt max and dP/dt min in hearts from normotensive and hypertensive animals, which were abolished in the presence of L-NAME, MDL and ODQ. In summary, the Bj-PROs induced endothelium-dependent vasorelaxation in rat thoracic aorta, coronary vasodilation and negative inotropic effects through mechanisms mediated by activation of nitric oxide pathway.

Comparison of Coronary Vasodilation and Systemic Hemodynamic Effect of Two Doses of Intracoronary Sodium Nitroprusside for Coronary Fractional Flow Reserve

Comparison of Coronary Vasodilation and Systemic Hemodynamic Effect of Two Doses of Intracoronary Sodium Nitroprusside for Coronary Fractional Flow Reserve

Quantitative Analysis of Vasodilatory Action of Quercetin on Intramural Coronary Resistance Arteries of the Rat In Vitro

BackgroundDietary quercetin improves cardiovascular health, relaxes some vascular smooth muscle and has been demonstrated to serve as a substrate for the cyclooxygenase enzyme.Aims1. To test quantitatively a potential direct vasodilatory effect on intramural coronary resistance artery segments, in different concentrations. 2. To scale vasorelaxation at different intraluminal pressure loads on such vessels of different size. 3. To test the potential role of prostanoids in vasodilatation induced by quercetin.MethodsCoronary arterioles (70–240 µm) were prepared from 24 rats and pressurized in PSS, using a pressure microangiometer.ResultsThe spontaneous tone that developed at 50 mmHg was relaxed by quercetin in the 10−9 moles/lit concentration (p<0.05), while 10−5 moles/lit caused full relaxation. Significant relaxation was observed at all pressure levels (10–100 mmHg) at 10−7 moles/lit concentration of quercetin. The cyclooxygenase blocker indomethacin (10−5moles/lit) induced no relaxation but contraction when physiological concentrations of quercetin were present in the tissue bath (p<0.02 with Anova), this contraction being more prominent in smaller vessels and in the higher pressure range (p<0.05, Pearson correlation). A further 2–8% contraction could be elicited by the NO blocker L-NAME (10−4 moles/lit).ConclusionThese results demonstrate that circulating levels of quercetin (10−7 moles/lit) exhibit a substantial coronary vasodilatory effect. The extent of it is commeasurable with that of several other physiological mechanisms of coronary blood flow control. At least part of this relaxation is the result of an altered balance toward the production of endogenous vasodilatory prostanoids in the coronary arteriole wall.

Angiotensin II type 1 receptor blockade restores angiotensin-(1–7)-induced coronary vasodilation in hypertrophic rat hearts

The aim of the present study was to investigate the coronary effects of Ang-(1-7) [angiotensin-(1-7)] in hypertrophic rat hearts. Heart hypertrophy was induced by abdominal aorta CoA (coarctation). Ang-(1-7) and AVE 0991, a non-peptide Mas-receptor agonist, at picomolar concentration, induced a significant vasodilation in hearts from sham-operated rats. These effects were blocked by the Mas receptor antagonist A-779. Pre-treatment with L-NAME (N(G)-nitro-L-arginine methyl ester) or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one) [NOS (NO synthase) and soluble guanylate cyclase inhibitors respectively] also abolished the effect of Ang-(1-7) in control hearts. The coronary vasodilation produced by Ang-(1-7) and AVE 0991 was completely blunted in hypertrophic hearts. Chronic oral administration of losartan in CoA rats restored the coronary vasodilation effect of Ang-(1-7). This effect was blocked by A-779 and AT2 receptor (angiotensin II type 2 receptor) antagonist PD123319. Acute pre-incubation with losartan also restored the Ang-(1-7)-induced, but not BK (bradykinin)-induced, coronary vasodilation in hypertrophic hearts. This effect was inhibited by A-779, PD123319 and L-NAME. Chronic treatment with losartan did not change the protein expression of Mas and AT2 receptor and ACE (angiotensin-converting enzyme) and ACE2 in coronary arteries from CoA rats, but induced a slight increase in AT2 receptor in aorta of these animals. Ang-(1-7)-induced relaxation in aortas from sham-operated rats was absent in aortas from CoA rats. In vitro pre-treatment with losartan restored the Ang-(1-7)-induced relaxation in aortic rings of CoA rats, which was blocked by the Mas antagonist A-779 and L-NAME. These data demonstrate that Mas is strongly involved in coronary vasodilation and that AT1 receptor (angiotensin II type 1 receptor) blockade potentiates the vasodilatory effects of Ang-(1-7) in the coronary beds of pressure-overloaded rat hearts through NO-related AT2- and Mas-receptor-dependent mechanisms. These data suggest the association of Ang-(1-7) and AT1 receptor antagonists as a potential therapeutic avenue for coronary artery diseases.

Diferencias y similitudes entre los bloqueadores de los receptores del calcio (a ntagonistas del calcio)

Calcium-channel blockers (CCB) are first-line treatment options for hypertension. Multiple studies have demonstrated their excellent blood-pressure-lowering activity, and a wide number of morbidity and mortality studies have shown these drugs to be able to revert subclinical organ damage such as left ventricular hypertrophy or microalbuminuria. Although most studies have been carried out with the dihydropyridine (DHP), amlodipine, several studies of morbidity and mortality support the use the non-DHP, verapamil, as a first-line agent. Non-DHPs provide a series of advantages such as their potent coronary vasodilator effect, an antiarrhythmic effect based on their negative chronotropic and inotropic properties, and a lower incidence of peripheral edema. Finally, their wide possibilities for combination with other first-line agents, such as renin-angiotensin system blockers, make calcium-channel blockers especially attractive.

Selective adenosine agonists and myocardial perfusion imaging

Selective adenosine receptor agonists have several advantages for use as stress agents in conjunction with myocardial perfusion imaging compared to the non selective agents such as adenosine and dipyridamole. This review will summarize the pre-clinical and clinical data on the selective adenosine agonist stress agents regadenoson (Lexiscan®), binodenoson (CorVue™) and apadenoson (Stedivaze™) that have been studied so far with focus on regadenoson that has the most clinical data published so far. The article will review the adenosine receptor types and properties. It will also review the various attributes of the selective adenosine agonists including their pharmacology, pharmacokinetics and pharmacodynamics, their coronary vasodilatory and hemodynamic effects, their safety and side effects, their interactions with other drugs and their use with myocardial perfusion imaging. The landmark trials of the selective adenosine agonists will be reviewed as well as their use in special patient populations undergoing stress myocardial perfusion imaging.

Nitric Oxide–mediated Relaxation to Lactate of Coronary Circulation in the Isolated Perfused Rat Heart

The objective of this study was to analyze the effects of lactate on coronary circulation. Rat hearts were perfused in a Langendorff preparation, and the coronary response to lactate (3-30 mM) was recorded after precontracting coronary vasculature with 11-dideoxy-1a,9a-epoxymethanoprostaglandin F2α (U46619), in the presence or the absence of the inhibitor of nitric oxide synthesis, N-omega-nitro-l-arginine methyl ester (l-NAME, 10 M), the blocker of Ca-dependent potassium channels, tetraethylammonium (TEA, 10 M), or the blocker of adenosine triphosphate-sensitive potassium channels, glybenclamide (10 M). The effects of lactate were also studied in isolated segments of rat coronary arteries that were precontracted with U46619, with or without endothelium. In perfused hearts, lactate induced concentration-dependent coronary vasodilatation and a reduction in myocardial contractility (left ventricular developed pressure and dP/dt) without altering the heart rate. Coronary vasodilatation in response to lactate was reduced by l-NAME but unaffected by TEA or glybenclamide. The effects of lactate on myocardial contractility were unchanged by l-NAME, TEA, or glybenclamide. In isolated coronary artery segments, lactate also produced relaxation, an effect attenuated by removing the endothelium. Together these findings suggest that lactate exerts coronary vasodilatory effects through the release of endothelial nitric oxide, independently of potassium channels. These findings may be relevant for the regulation of coronary circulation when lactate levels are elevated.

Aqueous-methanolic extract of sweet flag (Acorus calamus) possesses cardiac depressant and endothelial-derived hyperpolarizing factor-mediated coronary vasodilator effects

This investigation was aimed to probe the pharmacological base of medicinal use of Acorus calamus in ischemic heart diseases. Effect on heart parameters was studied in isolated rabbit heart while coronary vasodilator effect was studied in isolated bovine coronary arterial rings, suspended in tissue baths filled with Krebs solution, maintained at 37°C, aerated with carbogen and responses were measured on PowerLab data acquisition system. In Langendorrf's perfused rabbit heart, the crude extract of Acorus calamus (Ac.Cr) at 0.01-10 mg/mL partially suppressed force of ventricular contractions (FVC), heart rate (HR) and coronary flow (CF). The ethylacetate fraction completely suppressed FVC, partially suppressed HR and CF, while the nHexane fraction exhibited similar effect on FVC and HR but increased CF, similar to methacholine and arachidonic acid. In bovine coronary arterial preparations, Ac.Cr caused inhibition of U46619 (20 nM)-precontractions, which was blocked in presence of increasing concentration of K(+) (4.8-20 mM), tetraethylammonium (1 μM) and SKF525A (10 μM), similar to arachidonic acid and methacholine, indicating K(+) channels activation and possible involvement of endothelial-derived hyperpolarizing factor (EDHF). Activity-directed fractionation revealed that EDHF-mediated activity is concentrated in the nHexane fraction. When tested against high K(+), the ethylacetate fraction was found more potent than parent crude extract and nHexane fraction. These data indicate that Ac.Cr mediates coronary vasodilator effect primarily through EDHF, responsible for the increase in CF, while the cardiac depressant effects may be due to the presence of additional cardiac depressant constituent(s), thus provides possible mechanistic basis to its medicinal use in ischemic heart diseases.

Prostanoids suppress the coronary vasoconstrictor influence of endothelin after myocardial infarction

Myocardial infarction (MI) is associated with endothelial dysfunction resulting in an imbalance in endothelium-derived vasodilators and vasoconstrictors. We have previously shown that despite increased endothelin (ET) plasma levels, the coronary vasoconstrictor effect of endogenous ET is abolished after MI. In normal swine, nitric oxide (NO) and prostanoids modulate the vasoconstrictor effect of ET. In light of the interaction among NO, prostanoids, and ET combined with endothelial dysfunction present after MI, we investigated this interaction in control of coronary vasomotor tone in the remote noninfarcted myocardium after MI. Studies were performed in chronically instrumented swine (18 normal swine; 13 swine with MI) at rest and during treadmill exercise. Furthermore, endothelial nitric oxide synthase (eNOS) and cyclooxygenase protein levels were measured in the anterior (noninfarcted) wall of six normal and six swine with MI. eNOS inhibition with N(ω)-nitro-L-arginine (L-NNA) and cyclooxygenase inhibition with indomethacin each resulted in coronary vasoconstriction at rest and during exercise, as evidenced by a decrease in coronary venous oxygen levels. The effect of l-NNA was slightly decreased in swine with MI, although eNOS expression was not altered. Conversely, in accordance with the unaltered expression of cyclooxygenase-1 after MI, the effect of indomethacin was similar in normal and MI swine. L-NNA enhanced the vasodilator effect of the ET(A/B) receptor blocker tezosentan but exclusively during exercise in both normal and MI swine. Interestingly, this effect of L-NNA was blunted in MI compared with normal swine. In contrast, whereas indomethacin increased the vasodilator effect of tezosentan only during exercise in normal swine, indomethacin unmasked a coronary vasodilator effect of tezosentan in MI swine both at rest and during exercise. In conclusion, the present study shows that endothelial control of the coronary vasculature is altered in post-MI remodeled myocardium. Thus the overall vasodilator influences of NO as well as its inhibition of the vasoconstrictor influence of ET on the coronary resistance vessels were reduced after MI. In contrast, while the overall prostanoid vasodilator influence was maintained, its inhibition of ET vasoconstrictor influences was enhanced in post-MI remote myocardium.

Positive inotropic, positive chronotropic and coronary vasodilatory effects of rat amylin: mechanisms of amylin-induced positive inotropy

Even though there are a few studies dealing with the cardiac effects of amylin, the mechanisms of amylin-induced positive inotropy are not known well. Therefore, we investigated the possible signaling pathways underlying the amylin-induced positive inotropy and compared the cardiac effects of rat amylin (rAmylin) and human amylin (hAmylin).Isolated rat hearts were perfused under constant flow condition and rAmylin or hAmylin was infused to the hearts. Coronary perfusion pressure, heart rate, left ventricular developed pressure and the maximum rate of increase of left ventricular pressure (+dP/dtmax) and the maximum rate of pressure decrease of left ventricle (-dP/dtmin) were measured.rAmylin at concentrations of 1, 10 or 100 nM markedly decreased coronary perfusion pressure, but increased heart rate, left ventricular developed pressure, +dP/dtmax and -dP/dtmin. The infusion of H-89 (50 μM), a protein kinase A (PKA) inhibitor did not change the rAmylin (100 nM)-induced positive inotropic effect. Both diltiazem (1 μM), an L-type Ca2+ channel blocker and ryanodine (10 nM), a sarcoplasmic reticulum (SR) Ca2+ release channel opener completely suppressed the rAmylin-induced positive inotropic effect, but staurosporine (100 nM), a potent protein kinase C (PKC) inhibitor suppressed it partially. hAmylin (1, 10 and 100 nM) had no significant effect on coronary perfusion pressure, heart rate and developed pressure, +dP/dtmax and -dP/dtmin.We concluded that rAmylin might have been produced vasodilatory, positive chronotropic and positive inotropic effects on rat hearts. Ca2+ entry via L-type Ca2+ channels, activation of PKC and Ca2+ release from SR through ryanodine-sensitive Ca2+ channels may be involved in this positive inotropic effect. hAmylin may not produce any significant effect on perfusion pressure, heart rate and contractility in isolated, perfused rat hearts.

Incidence of Caffeine in Serum of Patients Undergoing Dipyridamole Myocardial Perfusion Stress Test by an Intensive Versus Routine Caffeine History Screening

The coronary vasodilatory effect of dipyridamole is competitively blocked by caffeine. The purposes of this study were to (1) assess the incidence of having detectable serum caffeine and (2) evaluate whether an intensive caffeine history screening strategy was superior to routine history screening before dipyridamole myocardial perfusion imaging. One hundred ninety-four patients who were randomized to an intensive or a routine screening history strategy were prospectively evaluated. Serum caffeine levels were determined in all patients. Outcomes data, including death, nonfatal myocardial infarction, and history of revascularization, were obtained at 24 months. Nearly 1 in 5 patients (19%) who screened negative by history had detectable serum caffeine. In patients who screened negative by history, there was no statistically significant difference in the percentage of caffeine seropositivity between the intensive and routine arms (16% vs 22%, respectively, p = 0.31). The incidence of combined end points of death, myocardial infarction, or revascularization was 22.9% and 7.3% in patients with and without detectable serum caffeine, respectively (p = 0.01). In conclusion, despite initial negative results on screening by history, a considerably high percentage of patients had positive serum caffeine levels. These results do not support the use of an intensive screening strategy. Detectable serum caffeine was associated with a higher incidence of adverse outcomes.

Effects of adenosine receptor agonists on guinea-pig isolated working hearts and the role of endothelium and NO.

The hypothesis that the coronary vasodilator effects of adenosine receptor agonists are independent of the vascular endothelium or mediators derived therefrom was examined in guinea-pig isolated working hearts. Adenosine receptor agonists, 5'-(N-ethylcarboxamido)-adenosine (NECA; two-fold selective for A2 over A1 receptors), 2-[p-(2-carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine (CGS21680; A2A selective), N6-cyclopentyl-adenosine (CPA; A1 selective) and N6-(3-iodobenzyl)adenosine-5'-N-methyluronamide (IB-MECA; A3 selective), were infused (3 x 10(-7) M) after endothelium removal by passing oxygen through the coronary circulation. In spontaneously beating hearts, CGS21680 and NECA increased, while CPA decreased, coronary flow. NECA and CPA reduced heart rate, left ventricular pressure and aortic output. The nitric oxide synthase (NOS) inhibitor, N(G)-nitro-L-arginine (L-NOARG; 3 x 10(-5) M) abolished the vasodilatation by NECA but not CGS21680, indicating that nitric oxide (NO) of a non-endothelial source mediated the NECA response. Coronary vasodilatation by CGS21680 was inhibited bythe A2A receptor antagonist, 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo [2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM241385). Indometacin (10(-6) M) attenuated the coronary vasodilatation to CGS21680, suggesting a partial role for cyclooxygenase products. IB-MECA had no effect, indicating no A3 receptor involvement. In paced working hearts, the responses were similar except CPA had no effect on coronary flow or aortic output and CGS21680 increased left ventricular pressure and the maximum rate of ventricular pressure rise. This study has demonstrated functionally effective removal of the endothelium by a novel method of passing oxygen through the coronary vasculature. A coronary vasodilator action of adenosine receptor agonists mediated via A2A receptors is endothelium- and NO-independent, but partially involves cyclooxygenase products.

Effect of Citrus paradisi extract and juice on arterial pressure both in vitro and in vivo

Citrus paradisi (grapefruit) consumption is considered as beneficial and it is popularly used for the treatment of a vast array of diseases, including hypertension. In the present study, the coronary vasodilator and hypotensive effects of Citrus paradisi peel extract were assessed in the Langendorff isolated and perfused heart model and in the heart and lung dog preparation. In both models, Citrus paradisi peel extract decreased coronary vascular resistance and mean arterial pressure when compared with control values (60 +/- 15 x 10(7) dyn s cm(-5) vs 100 +/- 10 x 10(7) dyn s cm(-5) and 90 mmHg vs 130 +/- 15 mmHg, respectively). These decreases in coronary vascular resistance and mean arterial pressure were blocked when isolated and perfused hearts and mongrel dogs were pre-treated with L-NAME. In humans, Citrus paradisi juice decreased diastolic arterial pressure and systolic arterial pressure both in normotensive and hypertensive subjects. Citrus paradisi juice produced a greater decrease in mean arterial pressure when compared with Citrus sinensis juice, cow milk and a vitamin C-supplemented beverage. However, more detailed studies are required to isolate, purify and evaluate the chemical compounds responsible for this pharmacological effect and to clarify its possible role for treating hypertension.

L’hémodilution ne modifie pas les effets vasodilatateurs coronariens de l’oxyde nitrique endogène ou exogène

It is well known that hemoglobin is a scavenger of nitric oxide (NO). The present study used a canine model to test the hypothesis that acute normovolemic hemodilution (ANH) affects NO-mediated coronary vasodilation. Studies were performed in 18 open-chest, anesthetized dogs. In Series 1, the contribution of endogenous NO to coronary vasodilatation during ANH with 5% dextran-40 (reduction in hematocrit by 50%) was assessed. This was accomplished by comparing myocardial blood flow (MBF; radioactive microspheres) in the left anterior descending (LAD) region, which was treated with the NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), to that in the circumflex (control) region. In Series 2, the LAD was perfused via a controlled-pressure extracorporeal system with coronary blood flow (CBF) measured with an ultrasonic, transit-time flow transducer. The dose-dependent increases in CBF caused by acetylcholine (ACh), which releases endogenous NO from the vascular endothelium, and sodium nitroprusside (SNP), which provides exogenous NO, were compared before and during ANH. Acute normovolemic hemodilution caused similar (approximately twofold) increases in MBF (P < 0.01) in the absence and presence of L-NAME, and it did not affect the dose-related increases in CBF caused by ACh and SNP. Series 1: under baseline conditions, hemoglobin in red blood cells does not limit the coronary vasodilatation resulting from tonic release of NO; NO does not mediate coronary vasodilation during ANH. Series 2: ANH does not influence the coronary vasodilating effects of increased levels of NO, whether due to endogenous release (ACh) or infusion of an NO donor (SNP).

Vulgarenol, a Sesquiterpene Isolated from Magnolia grandiflora, Induces Nitric Oxide Synthases II and III Overexpression in Guinea Pig Hearts

Vulgarenol, a sesquiterpene isolated from Magnolia grandiflora flower petals, decreased coronary vascular resistance in the Langendorff isolated and perfused heart model, when compared to the control group [(15.2 x 10(7) +/- 1.0 x 10(7)) dyn s cm(-5) vs. (36.8 x 10(7) +/- 1.2 x 10(7)) dyn s cm(-5)]. Our data suggest that this coronary vasodilator effect probably involved inducible and endothelial nitric oxide synthase overexpression (6.8 and 4.2 times over control, respectively), which correlated with increases in nitric oxide release [(223 +/- 9) pmol mL(-1) vs. (61 +/- 11) pmol mL(-1)] and in cyclic guanosine monophosphate production [(142 +/- 8) pmol mg(-1) of tissue vs. (44 +/- 10) pmol mg(-1) of tissue], as compared to control values. This effect was antagonized by 3 microm gadolinium(III) chloride, 100 microM N-nitro-L-arginine methyl ester, and 10 microM 1H-[1,2,4]oxadiazolo[4,2-a]quinoxalin-1-one. Hence, the vulgarenol-elicited coronary vasodilator effect could be mediated by the nitric oxide-soluble guanylyl cyclase pathway.

High-Resolution Transthoracic Echocardiography of the Left Anterior Descending Coronary Artery: A Novel Noninvasive Assessment of Coronary Vasoreactivity

The study objective was to determine the effects of salbutamol and nitroglycerin (NTG) on the luminal diameter of the left anterior descending (LAD) coronary artery, as measured noninvasively by the novel technique of high-resolution transthoracic echocardiography (HRTTE). Invasive studies of the coronary arteries have demonstrated vasodilatation by salbutamol and NTG. By using a novel technique of HRTTE, combined with assessment of augmentation index (AIx, a marker of peripheral arterial stiffness) by means of applanation tonometry from the radial artery (pulse wave analysis), we studied the vasomotion of the proximal LAD in healthy volunteers. Nineteen male subjects (age 31 +/- 5 years, mean +/- standard deviation) underwent HRTTE measurement of the wall thickness, luminal diameter, and external diameter of the proximal LAD, and AIx at baseline and 5, 10, 15, and 20 minutes after administration of inhaled salbutamol (400 microg) and, after return to baseline, sublingual NTG (300 microg). Salbutamol induced a 44% +/- 28% increase in LAD luminal diameter (2.8 +/- 0.8 mm to 3.7 +/- 0.9 mm, P < .001) and a reduction in AIx (-13.4% +/- 6.6%, P < .001). NTG induced greater changes in both parameters (60% +/- 30% increase in luminal diameter from baseline, 2.7 +/- 0.9 mm to 4.4 +/- 1.1 mm, P < .001; and reduction in AIx -24.1% +/- 8.2%, P < .001). Changes in LAD diameter and AIx were related after both salbutamol (r = -0.53, P = .02) and NTG (r = -0.57, P = .01). No significant change was detected in wall thickness. HRTTE is able to detect the LAD coronary artery vasodilating effects of NTG and salbutamol and correlates with peripheral vascular reactivity to these vasodilators. This approach provides a useful tool for the noninvasive assessment of coronary vasoreactivity.

Detection of moderate regional ischemia in pig hearts in vivo by near-infrared and thermal imaging: effects of dipyridamole

Effects of coronary vasodilator, dipyridamole, on epicardial oxygenation and flow were investigated under conditions of moderate coronary occlusion using near-infrared spectroscopic (NIRS) and thermal imaging. In anesthetized open chest pigs an inflatable occluder and flow probe were placed around the left anterior descending artery (LAD). In the ischemic group (n = 11) LAD occlusion (50% flow, 80 min) was followed by complete occlusion (10 min, n = 4), and reflow. Dipyridamole was infused (0.14 mg/min/kg/4 min) intravenously during 50% occlusion. In the control group (n = 6) LAD flow was temporarily increased (hyperemic response) by two 2-min periods of complete LAD occlusion applied 120 min apart, with a 4-min period of dipyridamole infusion between the two occlusions. NIRS and thermal images were acquired throughout the protocol. Maps of subepicardial oxygen saturation parameter (OSP), and epicardial temperature (T) were obtained. Partial occlusion reduced OSP and the temperature by 0.23 +/- 0.08 and 0.88 +/- 0.39 degrees C versus remote region, respectively. Dipyridamole decreased systolic blood pressure by 36%, which caused further decline in the LAD flow to 18% and OSP and T by 0.37 +/- 0.01 and 2.46 +/- 0.32 degrees C, respectively. Reflow restored OSP and T to their baseline levels. In control group dipyridamole and hyperemia increased LAD flow 2-4-fold associated with moderate increase in OSP and T. OSP and T showed linear dependence on the flow below 100%, which is leveled-off at flows above normal. Dipyridamole increases differences in the epicardial oxygenation and T between normal and moderately ischemic areas due to enhancement of disparity in perfusion of these areas.