Coronary Resistance Arteries Research Articles

Cyclosporine treatment preserves coronary resistance artery function in rat cardiac allografts

Background A marked decline in vascular myogenic response occurs during the course of rat cardiac allograft rejection. Two important contributory features are an inducible nitrous oxide synthase (iNOS)-catalyzed, NO-mediated vasodilation and a loss of smooth muscle function. In this study, we examine the effect of cyclosporine immunosuppressive therapy on the alleviation of arterial dysfunction of coronary resistance arteries in allografts using pressure myography. Methods Rats receiving heterotopic abdominal cardiac transplantation were treated with cyclosporine (5 mg/kg), Cremophore or distilled water. Coronary septal arteries (internal diameter 200 μm) were dissected from isograft (Lewis to Lewis) and allograft (Fisher to Lewis) rat hearts at Day 21 post-transplantation and mounted on a pressure myograph. Pressure-induced vasoconstriction was measured before and after iNOS inhibition with aminoguanidine (AG; 100 μmol/liter). Both endothelium-based (ACh-induced) and endothelium-independent (sodium nitroprusside–induced) vasorelaxation were also recorded in each group. Results Pressure-induced myogenic contraction was reduced in allograft coronary arteries at Day 21 post-transplantation compared with matched isografts ( p < 0.05). AG potentiated myogenic tone in allograft arteries, but had no effect on untreated Day 21 isograft vessels, indicating the presence of iNOS-based relaxation only in allograft vessels. Depolarization-induced vasoconstriction was lower in allograft compared with isograft arteries ( p < 0.05). Cyclosporine therapy also improved depolarization-induced constriction in allograft vessels compared with untreated groups ( p < 0.05). Furthermore, cyclosporine therapy preserved endothelium-based and endothelium-independent vasorelaxation in allograft arteries at Day 21 post-transplantation. Conclusions Cyclosporine immunosuppressive therapy has a significant effect on the alleviation of early endothelial and smooth muscle dysfunction in coronary allograft arteries.

Effects of left ventricular contractility and coronary vascular resistance on coronary dynamics.

Wave-intensity analysis, which separates upstream from downstream events and defines their interaction, has been used to study the effects of changes in left ventricular (LV) contractility (E(max)) and left circumflex coronary artery resistance (R(LCx)) on the coronary systolic flow impediment (CSFI). In 10 anesthetized, open-chest dogs, we measured coronary, aortic, and LV pressures, coronary velocity (Flowire), and flow. E(max) was increased by paired pacing and R(LCx) was modulated by intracoronary infusions of vasodilators (adenosine and nitroglycerin) and a vasoconstrictor (phenylephrine). When both E(max) and R(LCx) were varied, CSFI and the energy of the backward-going compression wave (I(W-)) were greatest at the highest levels of E(max) and the lowest levels of R(LCx). I(W-) was proportional to the CSFI. We conclude that contractility and coronary resistance change CSFI by modulating the backward-going compression wave.

Alterations in PKC signaling underlie enhanced myogenic tone in exercise-trained porcine coronary resistance arteries.

The intracellular mechanisms underlying enhanced myogenic contraction (MC) in coronary resistance arteries (CRAs) from exercise-trained (EX) pigs have not been established. The purpose of this study was to test the hypothesis that exercise-induced alterations in protein kinase C (PKC) signaling underlie enhanced MC. Furthermore, we sought to determine whether modulation of intracellular Ca(2+) signaling by PKC underlies enhanced MC in EX animals. Male Yucatan miniature swine were treadmill trained (n = 7) at approximately 75% of maximal O(2) uptake for 16 wk (6 miles/h, 60 min) or remained sedentary (SED, n = 6). Diameter measurements in response to intraluminal pressure (60, 75, and 90 cmH(2)O) or 60 mM KCl were determined in single, cannulated CRAs ( approximately 100 microm ID) with and without the PKC inhibitor chelerythrine (CE, 1 microM). Confocal imaging of Ca(2+) signaling [myogenic Ca(2+) (Ca(m))] was also performed in CRAs of similar internal diameter after abluminal loading of the Ca(2+) indicator dye fluo 4 (1 microM, 37 degrees C, 30 min). We observed significantly greater MC in CRAs isolated from EX than from SED animals at 90 cmH(2)O, as well as greater reductions in MC after CE at all pressures studied. At intraluminal pressures of 75 and 90 cmH(2)O, CE produced greater decreases in Ca(m) in CRAs from EX than from SED animals (64% vs. 25%, P < 0.05). Inhibition of KCl constriction and Ca(m) by CE was also greater in EX animals (P < 0.05). Western blotting revealed significant increases in Ca(2+)-dependent PKC-alpha ( approximately 50%) but not Ca(2+)-independent PKC-epsilon levels in CRAs isolated from EX animals (P < 0.05). We also observed significant group differences in phosphorylated PKC-alpha levels. Finally, voltage-gated Ca(2+) current (VGCC) was effectively blocked by CE, bisindolylmaleimide, and staurosporine in isolated smooth muscle cells from CRAs, providing evidence for a mechanistic link between VGCCs and PKC in our experimental paradigm. These results suggest that enhanced MC in CRAs from EX animals involves PKC-dependent modulation of intracellular Ca(2+), including regulation of VGCCs.

ACE inhibitors and statins acutely improve endothelial dysfunction of human coronary arterioles.

Long-term treatment with angiotensin-converting enzyme (ACE) inhibitors as well as angiotensin II type 1 (AT(1)) receptor antagonists and statins reduces cardiovascular mortality in patients with coronary artery disease as well as chronic heart failure. Little is known about the acute effects of these compounds on vascular reactivity of coronary resistance vessels. Coronary arterioles were obtained from patients undergoing coronary bypass operation (atherosclerosis group) or valve replacement (control group). Responses to endothelium-dependent agonists (histamine, serotonin, and acetylcholine) as well as to the endothelium-independent agonist sodium nitroprusside (SNP) were investigated under baseline conditions and after incubation (15 min) with lisinopril (ACE inhibitor), candesartan (AT(1) receptor antagonist), or fluvastatin. In atherosclerotic vessels, vasorelaxation was significantly reduced to all endothelium-dependent agonists but not, however, to SNP (77 +/- 8, -24 +/- 16, -46 +/- 24, and 98 +/- 8% relaxation for histamine, serotonin, acetylcholine, and SNP, respectively). Lisinopril and fluvastatin but not candesartan significantly improved the responses to the endothelium-dependent agonists (lisinopril: 94 +/- 4, 17 +/- 22, and -20 +/- 13%; fluvastatin: 96 +/- 8, 23 +/- 21, and -25 +/- 18% relaxation for histamine, serotonin, and acetylcholine, respectively). The effect of lisinopril was prevented by pretreatment with a bradykinin antagonist (HOE-130) and dichloroisocoumarine, an inhibitor of kinine-forming enzymes. Pretreatment with a nitric oxide (NO) synthase inhibitor abolished the improvement of endothelial function by lisinopril and fluvastatin. Vascular reactivity in the control group was not influenced by any of the pharmacological interventions. The data demonstrate that in atherosclerosis, endothelium-dependent relaxation of coronary resistance arteries is severely compromised. The impairment can acutely be reversed by ACE inhibitors and statins via increasing the availability of NO.

Effect of intracoronary estradiol on postischemic microvascular damage in a porcine model: a myocardial contrast echocardiographic study.

Coronary microvascular damage can occur in the presence of myocardial ischemia even if epicardial vessels are patent, a phenomenon known as "no-reflow." Estrogens have favorable effects on coronary conductance and resistance arteries, and may have therapeutic value in ischemic syndromes. Myocardial contrast echocardiography (MCE) is a promising method for evaluating microvascular damage. In this study, the authors hypothesized that acute intracoronary 17beta-estradiol administration can reduce postischemic microvascular damage, which is evaluated by MCE, in a porcine model. Sixteen male pigs were randomized into 2 groups: the treatment group (n = 9) received intracoronary estradiol in increasing doses, and the control group (n = 7) received intracoronary vehicle (dimethylsulfoxide, DMSO). Microvascular damage was induced by balloon catheter occlusion followed by reperfusion of the left circumflex coronary artery (LCX). MCE using Levovist with harmonic imaging was performed before and during 15-minute balloon occlusion of the proximal LCX to determine perfusion areas of the left anterior descending artery (LAD) and LCX. MCE was performed immediately postocclusion and after each injection of estradiol (1, 10, and 100 nmol/L) or DMSO. Videodensitometry measurements were performed as a quantitative marker for myocardial microvascular damage. Videodensitometry results were expressed as peak intensity ratios. Intracoronary estradiol induced a significant reduction in myocardial microvascular damage after ischemic episode by videodensitometry measurements when compared to intracoronary DMSO. The authors conclude that intracoronary injection of estradiol reduces postischemic microvascular damage measured by MCE in a porcine model.

Mitochondrial Sources of H 2 O 2 Generation Play a Key Role in Flow-Mediated Dilation in Human Coronary Resistance Arteries

We previously showed that hydrogen peroxide (H2O2) contributes to flow-induced dilation in human coronary resistance arteries (HCRAs); however, the source of this H2O2 is not known. We hypothesized that the H2O2 is derived from superoxide (O2*-) generated by mitochondrial respiration. HCRAs were dissected from right atrial appendages obtained from patients during cardiac surgery and cannulated with micropipettes. H2O2-derived radicals and O2*- were detected by electron spin resonance (ESR) using BMPO as the spin trap and by histofluorescence using hydroethidine (HE, 5 micromol/L) and dichlorodihydrofluorescein (DCFH, 5 micromol/L). Diameter changes to increases in pressure gradients (20 and 100 cm H2O) were examined in the absence and the presence of rotenone (1 micromol/L), myxothiazol (100 nmol/L), cyanide (1 micromol/L), mitochondrial complex I, III, and IV inhibitors, respectively, and apocynin (3 mmol/L), a NADPH oxidase inhibitor. At a pressure gradient of 100 cm H2O, ubisemiquinone and hydroxyl radicals were detected from effluents of vessels. Including superoxide dismutase and catalase in the perfusate reduced the ESR signals. Relative ethidium and DCFH fluorescence intensities in HCRAs exposed to flow were enhanced (1.45+/-0.15 and 1.57+/-0.12, respectively compared with no-flow) and were inhibited by rotenone (0.87+/-0.17 and 0.95+/-0.07). Videomicroscopic studies showed that rotenone and myxothiazol blocked flow-induced dilation (% max. dilation at 100 cm H2O: rotenone, 74+/-3% versus 3+/-13%; myxothiazol, 67+/-3% versus 28+/-4%; P<0.05). Neither cyanide nor apocynin altered flow-induced dilation. These results suggest that shear stress induced H2O2 formation, and flow-induced dilation is derived from O2*- originating from mitochondrial respiration.

Coronary endothelial function: The impact of aging in a matched study group with normal coronary arteries

Make Kelm Julius Rath, P&a Kleinbongard, Tienush Rassaf, Michael Preik, Bodo E. Strauer, Universitatsklinikum Diisseldorf, Diisseldorf, Germany Background: Nitric oxide (NO) has been shown to dilate vessels and to inhibit platelet function, both effects highly desirable during percutaneous intervention (PCI) in patients with coronary artery disease (CAD). Whether or not NO applied directly into human coro- nary circulation exerts biological effects is unknown so far. Therefore, the aims of our study were: (i) to develop a method for reproducible production of sterile solutions con- taining authentic NO, (ii) to find a save mode of intracoronary (ic.) application, and (iii) and to characterize potential dilatory effects in conduit and resistance coronary arteries. Methods: Changes in coronary blood flow (CBF) were quantified by quantitative coro- nary angiography (QCA) and intracoronary Doppler guide wares (ICD) in 13 patients with- out flow limiting CAD after application of either saline controls, aqueous NO solutions (NO.1 -6 wmol), adenosin (ADO, 2.4mg/min) or tsosorbiddinitrate (ISDN, 0.3 mg) in ran- dom order. Results: NO dilated epicardial arteries I” a dose-dependent manner up to lo+_1 %, equiv- alent to that seen upon ISDN. In parallel average peak velocity (APV) increased from 21 to 51+4 cm/s. Thus NO dilated coronary microvasculature to almost the same degree as seen after infusion of adenosine, whereas ISDN increased APV only slightly. Conse- quently. coronary blood flow increased according to the following rank order: NO and ADO > ISDN, whereas saline controls ware without effect. NO induced increases in CBF lasted much longer than expected from Its biochemical life span in human blood. Heart rate or blood pressure remained unaffected. Conclusions:Aqueous NO solutions can be applied directly into human coronary circu- lation and dilate uniformly epicardial

Two different coronary blood flow velocity patterns in thrombolysis in myocardial infarction flow grade 2 in acute myocardial infarction: Insight into mechanisms of microvascular dysfunction

ObjectivesWe sought to determine which of the two main potential mechanisms underlying Thrombolysis In Myocardial Infarction flow grade 2 (TIMI-2 flow) operate in an individual patient who has had an acute myocardial infarction (AMI). BackgroundSystolic flow reversal (SFR) is a specific finding of capillary damage, the no-reflow phenomenon. The coronary blood flow velocity (CBFV) pattern of thromboemboli, however, remains unknown. MethodsData on 105 patients with AMI (57 with anterior and 48 with nonanterior cases) who underwent a coronary intervention were analyzed. The CBFV was recorded by a Doppler guide wire, and tissue perfusion was assessed with myocardial contrast echocardiography (MCE). ResultsStudy patients were classified into three groups according to TIMI grade and the presence or absence of SFR: 1) TIMI-3 flow (n = 80); 2) TIMI-2 flow with SFR (SFR[+], n = 14); and 3) TIMI-2 flow without SFR (SFR[-], n = 11). Diastolic CBFV was the lowest in SFR(-) (TIMI-3 vs. SFR[+] vs. SFR[-]: 34 vs. 31 vs. 9 cm/s), and the systolic to diastolic CBFV ratio was also the highest in SFR(-) (0.43 vs. −0.18 vs. 0.66). The no-reflow phenomenon documented by MCE was found in all patients in the SFR(+) group, but in only one patient (10%) in the SFR(-) group. Intracoronary thrombus was more frequently found in SFR(-) than in SFR(+) (91% vs. 14%, p < 0.05). ConclusionsAt least two different CBFV patterns are noted in patients with reperfused AMI who have TIMI-2 flow. Capillary damage is mostly responsible for SFR(+), and SFR(-) is seen in thromboemboli possibly due to increased coronary arterial resistance.

Characteristics of coronary resistance artery function in a biracial cohort with severe left ventricular hypertrophy

Characteristics of coronary resistance artery function in a biracial cohort with severe left ventricular hypertrophy

Long-term effects of thiazolidinedione on vasomotion of resistance coronary arteries in type-2 diabetics

Long-term effects of thiazolidinedione on vasomotion of resistance coronary arteries in type-2 diabetics

N-terminal chromogranin-derived peptides as dilators of bovine coronary resistance arteries

N-terminal peptides of chromogranin A and B (CGA and CGB) were compared for dilator responses in isolated bovine coronary arteries (bCoA), measuring diameter changes as a function of pressure. bCoA developed and maintained myogenic tone (MYT) at ∼20% from 50 to 150 mm Hg. In contrast to CGB 1–40, CGA 1–40 and CGA 1–76 (VS-I) both displayed significant intrinsic vasodilator effects. CGA 1–40 reduced myogenic reactivity from 70 to 150 mm Hg ( p<0.05, n=6). At 75 mm Hg, CGA 1–40 showed a concentration-dependent dilatation at 0.1 nM–10 μM. The dilator effect of CGA 1–40 persisted at moderately elevated [K +] e (8.4–16 mM). However, this effect was diminished by pertussis toxin (PTX) and abolished by antagonists to several subtypes of K + channels (tetraethylammonium, Ba 2+ and glibenclamide). These results demonstrate that the N-terminal domain of CGA has dilator effect in the myogenically active bCoA. We propose that CGA 1–40 and the naturally occurring vasostatin I are regulatory peptides of relevance for the coronary microcirculation and that a G αi sub-unit and K + channel activation may be involved in the signal pathway.

The effects of levosimendan on myocardial oxygen consumption and coronary blood flow early after coronary artery bypass grafting

Levosimendan (LS) is a myocardial calcium sensitiser indicated for the treatment of acute decompensated heart failure. This randomised, double-blind trial evaluated the haemodynamic effects of LS in low-risk patients (n = 23) following coronary artery bypass surgery. The effects of LS on myocardial oxygen (O2) consumption, coronary blood flow and systemic haemodynamics were measured by thermodilution. Patients received LS, 8 μg/kg (n = 8), or LS, 24 μg/kg (n = 7), or placebo (n = 8) as a 5-min infusion 1 hour after surgery. Measurements of systemic and coronary sinus haemodynamics, myocardial O2 consumption and cardiac substrate utilisation were made, before and after treatment with LS. Levosimendan, 8 μg/kg and 24 μg/kg, significantly increased cardiac output (CO) by 0.7 and 1.6 l/min, respectively (P < 0.05), compared to baseline. Mean arterial pressure and pulmonary vascular resistance decreased significantly with both doses of LS, as did coronary artery resistance, the latter being indicative of coronary vasodilation (P < 0.05). Furthermore, an increase in coronary blood flow of 28 ml/min and 42 ml/min with LS, 8 μg/kg and 24 μg/kg, respectively, was obtained (P = 0.054 for both doses combined). Despite the markedly improved cardiac function seen with LS, neither dose significantly increased myocardial O2 consumption compared with placebo. In addition, no significant differences in myocardial free fatty acid, lactate, pyruvate and glucose utilisation were observed in LS-treated patients compared to placebo controls. In conclusion, based on the results of this study, LS may be of significant benefit in improving cardiac function in patients with low CO following coronary artery bypass surgery, with no significant increase in O2 consumption.

Coronary Endothelium-Dependent and Independent Vasomotor Responses in Patients With Hypertrophic Cardiomyopathy

It is well known that coronary flow reserve (CFR) is decreased in patients with hypertrophic cardiomyopathy (HCM), but it is unclear whether coronary endothelial function is impaired. Coronary endothelial function and CFR in the coronary macro- and microcirculation was evaluated in 14 patients with HCM and 11 control subjects. Acetylcholine (ACh), bradykinin (BK) and papaverine were infused into the left coronary artery. Coronary cross-sectional area was determined by quantitative coronary angiography and coronary blood flow (CBF) was determined by the product of the coronary cross-sectional area and CBF velocity measured by an intracoronary Doppler guidewire. Acetylcholine at 100 microg induced diffuse coronary spasms of the left anterior descending coronary arteries in 3 of the patients with HCM. The changes in the diameter of the left anterior descending coronary artery and the increases in CBF induced by BK (0.2, 0.6, and 2.0 microg/min) did not differ between the 2 groups. CFR was lower in the HCM group than in the control group (p<0.01). Moreover, the ratio of BK-induced CBF increase to papaverine-induced CBF increase was comparable between the 2 groups. Endothelium-dependent vasodilation of the epicardial and resistance coronary arteries induced by BK was preserved despite the decreased CFR in patients with HCM.

Magnesium causes nitric oxide independent coronary artery vasodilation in humans

OBJECTIVETo determine how magnesium affects human coronary arteries and whether endothelium derived nitric oxide (EDNO) is involved in the coronary arterial response to magnesium.DESIGNQuantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthase inhibitorNG-monomethyl-L-arginine (L-NMMA) on magnesium induced dilation of the epicardial and resistance coronary arteries.SETTINGHiroshima University Hospital a tertiary cardiology centre.PATIENTS17 patients with angiographically normal coronary arteries.INTERVENTIONSMagnesium sulfate (MgSO4) (0.02 mmol/min and 0.2 mmol/min) was infused for two minutes into the left coronary ostium before and after intracoronary infusion of L-NMMA.MAIN OUTCOME MEASURESDiameter of the proximal and distal segments of the epicardial coronary arteries and coronary blood flow.RESULTSAt a dose of 0.02 mmol/min, MgSO4 did not affect the coronary arteries. At a dose of 0.2 mmol/min, MgSO4 caused coronary artery dilation (mean (SEM) proximal diameter 3.00 (0.09) to 3.11 (0.09) mm; distal 1.64 (0.06) to 1.77 (0.07) mm) and increased coronary blood flow (79.3 (7.5) to 101.4 (9.9) ml/min, p &lt; 0.001 vbaseline for all). MgSO4 increased the changes in these parameters after the infusion of L-NMMA (p &lt; 0.001v baseline).CONCLUSIONSMagnesium dilates both the epicardial and resistance coronary arteries in humans. Furthermore, the coronary arterial response to magnesium is dose dependent and independent of EDNO.

Effects of red wine, alcohol, and quercetin on coronary resistance and conductance arteries.

Moderate consumption of alcoholic beverages is associated with a reduced risk of coronary heart disease (CHD). Some evidence suggests that red wine is particularly beneficial in this regard and may account in part for the French paradox, although the mechanism of this effect is unknown. We assessed the effects of red wine, ethanol, and quercetin, a major flavonoid constituent of red wine, in coronary resistance vessels (80-150 microm, i.d.) and conductance vessels (300-525 microm, i.d.) of the rabbit. Vessel wall tension was measured in isolated segments maintained in a wire-type myograph (37 degrees C) and preconstricted with 30 mM K+. At an alcohol concentration (14 mM) equivalent to moderate consumption, red wine evoked a small, transient constrictor effect in resistance and conductance vessels (9+/-4%, n = 5; 8+/-1%, n = 7, respectively; p < 0.05). Ethanol alone at this concentration was without effect. Quercetin (5.6, 8, and 30 microM) significantly relaxed resistance (-32+/-4%, n = 10; -47+/-2%, n = 7; -82+/-6%, n = 8, respectively) and conductance (-20+/-3%, n = 8; -32+/-4%, n = 8; -72+/-7%, n = 8, respectively) coronary arteries. Vasorelaxation by quercetin was endothelium-independent and was significantly greater in resistance than in conductance vessels. These data suggest that red wine and ethanol do not evoke relaxation in small coronary arteries at concentrations associated with moderate consumption. Quercetin elicits marked coronary vasorelaxation that is endothelium-independent. However, the concentrations of quercetin necessary to achieve this action are not attained with moderate red wine consumption.

Mechanisms of coronary artery depolarization by uridine triphosphate.

We sought to define the basic mechanisms by which pyrimidine nucleotides constrict rat coronary resistance arteries. Uridine triphosphate (UTP) caused a dose-dependent constriction in coronary arteries stripped of endothelium. UTP also depolarized and increased cytosolic Ca2+ in coronary smooth muscle cells. Nisoldipine, an antagonist of voltage-operated Ca2+ channels, blocked the rise in cytosolic Ca2+ and reduced UTP-induced vasoconstriction by approximately 75% which suggests a prominent role for depolarization in this constrictor response. The ionic basis of UTP-induced depolarization was subsequently explored in coronary smooth muscle cells using whole-cell patch-clamp electrophysiology. In the absence of K+ and with CsCl in the pipette, UTP (40 microM) activated a sustained inwardly rectifying current (-0.66 +/- 0.10 pA/pF at -60 mV). A 100 mM reduction in bath Na+ shifted the reversal potential of this current (from -2 +/- 1 to -28 +/- 4 mV) and reduced the magnitude (from -2.26 +/- 0.61 to -0.51 +/- 0.11 pA/pF). In addition to activating a depolarizing cation current, UTP inhibited hyperpolarizing outward currents. Specifically, UTP inhibited ATP-sensitive and voltage-dependent K+ currents yet had no effect on inwardly rectifying and Ca2+-activated K+ channels. This study indicates that electromechanical coupling is integral to pyrimidine-induced constriction in coronary resistance arteries.

Physiological antagonism of endothelin-1 in human conductance and resistance coronary artery.

The ability of four endogenous vasodilators, nitric oxide (NO; 0.01 - 30 microM), atrial (ANP), brain (BNP) and C-type (CNP) natriuretic peptide (0.1 - 300 nM), to reverse endothelin-1 (ET-1; 10 nM) constrictions in human resistance and conductance coronary arteries (CA) in vitro was investigated. ET-1 (0.1 - 300 nM) constricted resistance CA more potently than conductance CA (P<0.05; EC(50) values 2.98 nM (95% CI: 1.49 - 5.95 nM and 8.58 (4.72 - 15.6 nM) respectively)). The NO-donor diethylamine NONOate fully reversed the ET-1 constriction in conductance CA (E(MAX) 127+/-9.16%), however only partial reversal was observed in resistance CA (E(MAX) 78.8+/-8.13; P<0.05). The soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (100 microM) reduced the maximum response to diethylamine NONOate to 76.9+/-14.4% in conductance CA (P<0.05), but had no effect on resistance CA (E(MAX) 77.2+/-18.4%). There was no difference between responses to ANP in conductance and resistance CA (EC(50) values 4.25 nM (0.84 - 21.4 nM) and 18.4 nM (2.92 - 116 nM), E(MAX) 53.1+/-14.7% and 48.6+/-11.8% respectively). BNP was a more potent vasodilator of conductance than resistance CA. In conductance CA the mean EC(50) value was 2.4 nM (0.74 - 7.75 nM), E(MAX) 54.5+/-14.9%. Concentration-response curves to BNP were incomplete in resistance CA. Concentration-response curves to CNP were incomplete in both conductance and resistance CA. The greater potency of ET-1 in resistance vessels may exacerbate the effects of increased circulating levels of the peptide in disease. Only NO could fully reverse ET-1 mediated constrictions in conductance CA, and none of the dilators tested could completely counteract constrictions in resistance CA.

Preparation of Intramural Small Coronary Artery and Arteriole Segments and Resistance Artery Networks from the Rat Heart for Microarteriography and for in Situ Perfusion Video Mapping

Preparation of Intramural Small Coronary Artery and Arteriole Segments and Resistance Artery Networks from the Rat Heart for Microarteriography and for in Situ Perfusion Video Mapping

Coronary vasomotor responses to bradykinin and acetylcholine in patients with coronary spastic angina.

It is unclear whether coronary endothelial function is linked to the pathogenesis of coronary spastic angina (CSA), so the present study examined the coronary vasomotor responses to acetylcholine (ACh) and bradykinin (BK) in 23 patients with CSA, 26 patients with CSA+coronary artery disease (CAD), and 21 control patients. Acetylcholine induced vasospasm of the left coronary artery in all of the patients with CSA, but not in any of the control patients. The changes in dilatation of the left coronary artery in response to bradykinin at doses of 0.2, 0.6 and 2.0 microg/min in the CSA group were significantly greater than those in the other 2 groups. The ratio of epicardial coronary vasodilations induced by BK to those induced by nitroglycerin did not differ among any of the groups. Bradykinin caused a similar increase in coronary blood flow in the control group and CSA group, but had less of an effect in the CSA+CAD group. In conclusion, the vasorelaxing effect of BK was preserved not only in epicardial spasm coronary arteries induced by ACh, but also in resistance coronary arteries distal to the spasm arteries in patients with CSA. The coronary vasodilation response induced by BK may not deteriorate until coronary atherosclerosis advances in patients with CSA.

Vasodilator responses of coronary conduit and resistance arteries to continuous nitroglycerin infusion in humans: a Doppler guide wire study.

To examine the responses of coronary conduit and resistance arteries to the continuous i.v. administration of nitroglycerin in 15 patients with atypical chest pain, we measured coronary blood flow velocity in the left anterior descending coronary artery using a Doppler guide wire and the lumen diameter and cross-sectional area by quantitative coronary angiography. Systolic flow, diastolic flow, total coronary flow, and coronary vascular resistance were calculated. Stepwise increases in dose of nitroglycerin resulted in significant dose-dependent decrease in mean aortic pressure (p < 0.01) and increase in lumen diameter (p < 0.05). After nitroglycerin administration of 0.5 microg/kg/min, systolic flow decreased significantly by 89.9+/-15.7% (p < 0.01), and diastolic flow increased significantly by 74.2+/-37.1% (p < 0.05). Total coronary flow did not change significantly with the various doses of nitroglycerin. However, coronary vascular resistance decreased significantly at concentrations greater than 0.5 microg/kg/min nitroglycerin. Continuous nitroglycerin infusion did not reduce either diastolic or total coronary blood flow despite a significant reduction in coronary perfusion pressure. These results indicate that subendocardial blood flow might be maintained during continuous i.v. infusion of nitroglycerin within the clinical dose range.