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Biomedical subjects

Minoru Horie

Publications and source records attributed to Minoru Horie.

At least 55 records · Page 3Linked to original sources
PubMed2005

Inhibition of aldosterone and endothelin-1 by carperitide was attenuated with more than 1 week of infusion in patients with congestive heart failure.

Short-term infusion of carperitide (atrial natriuretic peptide) has beneficial effects on neurohumoral factors; however, it remains unclear whether the effects are sustained for long-term infusion. To evaluate the effects of long-term infusion of carperitide on neurohumoral factors in patients with chronic congestive heart failure (CHF), we measured neurohumoral factors before and 1 hour after stopping carperitide infusion in 42 CHF patients. Carperitide infusion was continued for more than 2 days until there was symptomatic improvement of CHF. Patients were divided into 2 groups by the median value of infusion duration: group 1 (less than 7 days, n=21) and group 2 (more than 7 days, n=21). In group 1, aldosterone (ALD) and endothelin-1 (ET-1) were significantly increased after stopping carperitide. In contrast, ALD and ET-1 did not change after stopping carperitide in group 2. The molar ratio of cyclic guanosine monophosphate/atrial natriuretic peptide before stopping carperitide was significantly lower in group 2 than in group 1. Suppression of ALD and ET-1 was maintained for 7 days of carperitide infusion, but the beneficial effect on neurohumoral factors was attenuated after more than 7 days, probably through down-regulation of biologic receptors coupled with guanylate cyclase in CHF patients.

Aldosterone↗
PubMed2005

Refractory gradient is responsible for the increase in ventricular vulnerability under sodium channel blockade.

BACKGROUND: Previous studies have shown that sodium channel (I(Na)) blockade increases ventricular vulnerability; however, there were differences in the degree of the increase. Because the vulnerable window (VW) is altered by the type of preshock refractory gradient (RG), the hypothesis was that the differences in the arrhythmogenesis of I(Na) blockade result from the different types of preshock RG employed. METHODS AND RESULTS: Simulations of regio(Na)l electric shock following constant pacing stimuli in 2-dimensional bidomain myocardial sheets under I(Na) blockade were conducted using 3 types of preshock RG: longitudinally tilted (LRG), transversely tilted (TRG), and non-tilted RG (NRG). The increase in the degree of I(Na) blockade almost linearly decreased the conduction velocity. The action potential duration in the LRG and TRG cases was non-linearly shortened with the increase in INa blockade because of electrotonic influences, whereas in the case of NRG it was slightly prolonged. In both LRG and TRG cases, the VW for reentry induction by electric shock was considerably widened by the INa blockade; however, this was not the case for NRG in which the VW was rather narrowed by the INa blockade. CONCLUSION: The type of preshock RG alters the degree of the increase in ventricular vulnerability under INa blockade.

Action Potentials↗
PubMed2005

Myocardial creatine concentration in various nonischemic heart diseases assessed by 1H magnetic resonance spectroscopy.

BACKGROUND: Previous (31)P magnetic resonance spectroscopy (MRS) studies demonstrated that the myocardial phosphocreatine-to-ATP ratio offered important information concerning the degree of dysfunction and prognosis in patients with cardiomyopathy. In the present study, we investigated total creatine (CR) levels in various diseased hearts using 1H MRS. METHODS AND RESULTS: Fourteen patients with the following conditions were examined: cardiac amyloidosis (n = 2); hypertensive heart disease (4); valvular disease (2); hypertrophic cardiomyopathy (2); dilated cardiomyopathy (2); restrictive cardiomyopathy (1); and post-operative atrial septal defect (1). Myocardial CR was measured using 1H MRS with point-resolved spectroscopy localization. Overall, myocardial CR levels in diseased hearts were significantly lower than those in the control group [16.5+/-6.0 (n = 14) vs 27.1+/-3.2 micromol/g (n = 10), p < 0.001]. There was a positive correlation between myocardial CR and left ventricular ejection fraction (42.9+/-13.8%, range 19.5-69.1%) despite the different mechanisms of cardiac dysfunction (r = 0.60, p < 0.05). Myocardial CR levels in patients who were hospitalized due to heart failure within 1 year were significantly lower than those in other patients [11.3+/-1.0 (n = 4) vs 18.6+/-5.9 micromol/g (n = 10), p < 0.05]. CONCLUSIONS: Noninvasive measurement of myocardial CR using 1H MRS may be valuable in the assessment of disease severity and prediction of clinical course in various forms of heart disease.

Adult↗
PubMed2005

Brachial artery flow-mediated vasodilation is correlated with coronary vasomotor and fibrinolytic responses induced by bradykinin.

Endothelium plays a key role in the regulation of not only vascular tone but also thrombosis and fibrinolysis. Brachial flow-mediated vasodilation (FMD) provides a noninvasive method of assessing coronary endothelial dysfunction. However, no data are available on the relationship between brachial FMD and coronary fibrinolytic activity. Thus, we examined the relationship between brachial FMD and coronary vasomotor and fibrinolytic function. Brachial FMD by reactive hyperemia was defined as a change in diameter relative to the baseline as measured using high-resolution ultrasound. Coronary blood flow (CBF) responses to bradykinin (BK) were analyzed using Doppler flow velocity measurement. Coronary release of tissue-type plasminogen activator (tPA) antigen was determined as the transcardiac tPA gradient x [CBF x (100 - hematocrity 100)]. In 77 patients with normal coronary arteries, BK caused dose-dependent increases in CBF, transcardiac tPA gradient, and coronary tPA release. Among them, brachial FMD, the BK-induced CBF increase, and the coronary tPA release induced by BK in 14 diabetic subjects were lower than those in 63 non-diabetic subjects (p < 0.05, respectively). Brachial FMD correlated with the CBF increase, transcardiac tPA gradient (0.2 microg/min: r = 0.25; 0.6 microg/min: r = 0.43; 2.0 microg/min: r = 0.34; p < 0.05, respectively), and coronary tPA release (0.2 microg/min: r = 0.24; 0.6 microg/min: r = 0.44; 2.0 microg/min: r = 0.32; p < 0.05, respectively) in response to BK. Brachial FMD correlated significantly with coronary endothelial function and fibrinolytic activity in response to BK. Type 2 diabetes impaired coronary and brachial endothelium-dependent vasodilation and coronary fibrinolytic activity.

Adult↗
PubMed2005

Combined analysis of polymorphisms in angiotensinogen and adducin genes and their effects on hypertension in a Japanese sample: The Shigaraki Study.

We examined the interactions between lifestyle and polymorphisms of salt-sensitive genes and their effects on hypertension in a general Japanese sample (The Shigaraki Study). The study group consisted of 2,902 subjects who underwent a medical examination in 1999 in Shigaraki, a suburban area in Shiga. Among 1,647 subjects not receiving antihypertensive medication, in a combined analysis of angiotensinogen (AGT) and adducin (ADD1) polymorphisms, double homozygosity of 235Thr or 460Trp was not found to be associated with hypertension. A multiple logistic regression analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [95% CI]: 1.06-1.08), body mass index (BMI) (OR: 1.18, 95% CI: 1.13-1.23), alcohol consumption (OR: 1.39, 95% CI: 1.16-1.66), family history of hypertension (OR: 1.57, 95% CI: 1.18-2.07), and combined AGT M235T Thr/Thr and ADD1 Trp/Trp polymorphisms (OR: 1.37, 95% CI: 1.03-1.82) were associated with hypertension. However, there was no interaction between eating salty food and combined AGT and ADD1 polymorphisms. Furthermore, eating salty food was not associated with hypertension in a multivariate analysis. Therefore, a combination of the AGT and ADD1 polymorphisms appears to be associated with hypertension. However, a simple questionnaire regarding salt intake was not sufficient to confirm the relationship between salt intake and hypertension and/or salt-sensitive genes.

Adult↗
PubMed2004

Plasma level of oxidized low-density lipoprotein is an independent determinant of coronary macrovasomotor and microvasomotor responses induced by bradykinin.

OBJECTIVES: We examined the relationship between coronary endothelium-dependent vasodilation in response to bradykinin (BK) and plasma levels of oxidized low-density lipoprotein (oxLDL) in subjects with normal coronary arteries. BACKGROUND: It is unclear whether the plasma oxLDL level is a determinant of coronary endothelial function. Bradykinin plays an important role in regulating resting coronary tone and flow-mediated coronary vasomotion. METHODS: Coronary blood flow (CBF) in the left anterior descending (LAD) coronary artery was assessed by quantitative angiography and a Doppler flow wire in 94 consecutive subjects with normal coronary arteries. The plasma oxLDL level was measured by enzyme-linked immunosorbent assay using DLH3R, a specific antibody against oxLDL. RESULTS: Plasma levels of oxLDL in diabetic subjects (n = 13) were higher than those in non-diabetic subjects (n = 81). Plasma levels of oxLDL correlated with body mass index (BMI). Bradykinin at doses of 0.2, 0.6, and 2.0 microg/min caused dose-dependent increases in diameter and CBF in the LAD coronary artery. By a univariate analysis, oxLDL levels significantly correlated with epicardial (r = -0.30, p < 0.0001) and resistant (r = -0.36, p = 0.003) coronary vasodilator responses to BK at 2.0 microg/min, whereas total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides were not associated with these coronary responses. In a stepwise multivariate analysis, oxLDL levels were significantly correlated with epicardial and resistant coronary vasomotor responses to BK, independent of age, gender, smoking status, other lipid levels, BMI, hypertension, and diabetes. CONCLUSIONS: The plasma level of oxLDL is an appropriate surrogate for assessing coronary endothelial-dependent vasomotor function as estimated by responses to BK compared with conventional risk factors for atherosclerosis.

Adult↗
PubMed2004

Mutation site-specific differences in arrhythmic risk and sensitivity to sympathetic stimulation in the LQT1 form of congenital long QT syndrome: multicenter study in Japan.

OBJECTIVES: We sought to compare the arrhythmic risk and sensitivity to sympathetic stimulation of mutations located in transmembrane regions and C-terminal regions of the KCNQ1 channel in the LQT1 form of congenital long QT syndrome (LQTS). BACKGROUND: The LQT1 syndrome is frequently manifested with variable expressivity and incomplete penetrance and is much more sensitive to sympathetic stimulation than the other forms. METHODS: Sixty-six LQT1 patients (27 families) with a total of 19 transmembrane mutations and 29 patients (10 families) with 8 C-terminal mutations were enrolled from five Japanese institutes. RESULTS: Patients with transmembrane mutations were more frequently affected based on electrocardiographic (ECG) diagnostic criteria (82% vs. 24%, p < 0.0001) and had more frequent LQTS-related cardiac events (all cardiac events: 55% vs. 21%, p = 0.002; syncope: 55% vs. 21%, p = 0.002; aborted cardiac arrest or unexpected sudden cardiac death: 15% vs. 0%, p = 0.03) than those with C-terminal mutations. Patients with transmembrane mutations had a greater risk of first cardiac events occurring at an earlier age, with a hazard ratio of 3.4 (p = 0.006) and with an 8% increase in risk per 10-ms increase in corrected Q-Tend. The baseline ECG parameters, including Q-Tend, Q-Tpeak, and Tpeak-end intervals, were significantly greater in patients with transmembrane mutations than in those with C-terminal mutations (p < 0.005). Moreover, the corrected Q-Tend and Tpeak-end were more prominently increased with exercise in patients with transmembrane mutations (p < 0.005). CONCLUSIONS: In this multicenter Japanese population, LQT1 patients with transmembrane mutations are at higher risk of congenital LQTS-related cardiac events and have greater sensitivity to sympathetic stimulation, as compared with patients with C-terminal mutations.

Adolescent↗
PubMed2004

Assessment of myocardial creatine concentration in dysfunctional human heart by proton magnetic resonance spectroscopy.

Creatine depletion in the non-viable infarcted human heart was previously demonstrated with proton magnetic resonance (MR) spectroscopy (1H MRS). In the present study, we assessed total creatine (CR) in human hearts with non-ischemic dysfunctions such as cardiomyopathy. Using cardiac-gated 1H MRS with MR image-guided PRESS localization, we measured septal CR in healthy and diseased human hearts. Fifteen patients with chronic heart failure (CHF, left ventricular ejection fraction < 45%) and 14 age-matched normal subjects were examined. Myocardial CR was significantly (p < 0.001) lower in failing hearts (15.1+/-SD 5.0 micromol/g wet weight, range 8.0-22.9) than in normal hearts (27.6+/-4.1 micromol/g wet weight, range 20.8-36.2). Myocardial CR concentrations in six heart failure patients with plasma B-type natriuretic peptide (BNP) levels of > 200 pg/ml (11.5+/-0.9 micromol/g wet weight, range 9.9-12.3) were significantly lower than those in four heart failure patients with plasma BNP levels of < 200 pg/ml (19.8+/-2.5 micromol/g wet weight, range 17.7-22.9, p < 0.001). Thus, our study showed that myocardial CR was decreased in non-ischemic dysfunctional hearts. Noninvasive measurements of myocardial CR by 1H MRS may be useful in the assessment of the severity of heart failure.

Creatine↗
PubMed2004

Transcardiac increase in tumor necrosis factor-alpha and left ventricular end-diastolic volume in patients with dilated cardiomyopathy.

BACKGROUND: It remains unclear whether tumor necrosis factor (TNF)-alpha and interleukin-6 (IL-6) are secreted from the failing heart and whether there is a relationship between the transcardiac gradients of these cytokines and left ventricular (LV) remodeling. AIMS: This study evaluated the relationship between transcardiac gradients of cytokines and LV volume and function in congestive heart failure patients with dilated cardiomyopathy (DCM). METHODS AND RESULTS: We measured the plasma levels of TNF-alpha and IL-6 in the aortic root (Ao) and the coronary sinus (CS) in 60 patients with DCM. There was no difference in plasma IL-6 between the Ao and the CS. However, the plasma TNF-alpha level was significantly higher in the CS than that in the Ao. There was a significant correlation between the transcardiac gradient of plasma TNF-alpha and the LV end-diastolic volume index (LVEDVI) and LV ejection fraction. According to stepwise multivariate analyses, the transcardiac increase of TNF-alpha showed an independent and significantly positive relationship with a large LVEDVI. CONCLUSIONS: These results indicate that the elevated plasma TNF-alpha is partly derived from the failing heart in patients with DCM and that TNF-alpha plays a potential role in structural LV remodeling in patients with DCM.

Adult↗
PubMed2004

Prognostic value of ECG-gated thallium-201 single-photon emission tomography in patients with coronary artery disease.

BACKGROUND: The phenomenon of reversible impairment in LV function has been well described and is known as myocardial stunning. OBJECTIVE: Thallium-201 myocardial perfusion gated SPECT was used to evaluate myocardial stunning and its incremental prognostic value in patients with coronary artery disease. PATIENTS AND METHODS: Fifty-six patients (aged 63+/-11 years) with coronary artery disease were included in this study. All subjects underwent exercise thallium scintigraphy. ECG-gated SPECT was obtained both at post-stress (10 minutes after the injection of 111 MBq of thallium at the time of peak exercise) and at rest (180 minutes). The left ventricular ejection fraction (LVEF) and end-systolic and end-diastolic volume (ESV, EDV) were determined by a quantitative gated SPECT (QGS) program. RESULTS: Follow-up was complete in all patients (mean 569 days). The magnitude of the depression of post-stress LVEF relative to the rest LVEF was correlated with the severity of ischemia (p < 0.05). The group with a median LVEF of more than 45% had a significantly higher event-free rate (p < 0.01). CONCLUSION: Assessment of post-stress left ventricular function by gated-SPECT provides incremental prognostic information and is useful in predicting cardiac events in patients with suspected or definite coronary artery disease.

Causality↗
PubMed2004

Visual assessment of coronary artery stenosis with electrocardiographically-gated multislice computed tomography.

BACKGROUND: With faster image acquisition times and thinner slice widths, multislice detector computed tomography (MSCT) allows visualization of human coronary arteries. Significantly improved image quality, with high resolution and new software for three-dimensional post-processing, has made noninvasive examination of the cavities within human body possible. OBJECTIVE: The aims of this study are to evaluate the diagnostic accuracy of ECG-gated MSCT for the detection of significant coronary artery stenosis and occlusions. METHODS: In 25 patients (19 male and 6 female aged 65+/-9 years) with suspected obstructive coronary artery disease, ECG-gated MSCT angiography was performed with an 8-slice MSCT scanner. Visual coronary arteries were simulated in three coronary arteries. Conventional coronary angiographies were performed in all patients. And coronary lesions in MSCT were estimated by two observers, who did not know the results of the coronary angiography. RESULTS: Current MSCT allows visual coronary artery with good image quality. The overall sensitivity for diagnosing significant coronary stenosis were 75.0%, the specificity was 95.6%. The positive and negative predictive values were 84.9 and 92.2%, respectively. The accuracy of MSCT for detecting coronary stenosis is the highest in the left main tranck and left anterior descending coronary artery, and lowest in the circumflex coronary artery. CONCLUSION: MSCT was feasible for the detection of coronary artery stenosis.

Adult↗
PubMed2004

Additional gene variants reduce effectiveness of beta-blockers in the LQT1 form of long QT syndrome.

INTRODUCTION: Beta-blockers are widely used to prevent the lethal cardiac events associated with the long QT syndrome (LQTS), especially in KCNQ1-related LQTS (LQT1) patients. Some LQT1 patients, however, are refractory to this therapy. METHODS AND RESULTS: Eighteen symptomatic LQTS patients (12 families) were genetically diagnosed as having heterozygous KCNQ1 variants and received beta-blocker therapy. Cardiac events recurred in 4 members (3 families) despite continued therapy during mean follow-up of 70 months. Three of these patients (2 families) had the same mutation [A341V (KCNQ1)]; and the other had R243H (KCNQ1). The latter patient took aprindine, which seemed to be responsible for the event. By functional assay using a heterologous mammalian expression system, we found that A341V (KCNQ1) is a loss-of-function type mutation (not dominant negative). Further genetic screening revealed that one A341V (KCNQ1) family cosegregated with S706C (KCNH2) and another with G144S (KCNJ2). Functional assay of the S706C (KCNH2) mutation was found to reduce the current density of expressed heterozygous KCNH2 channels with a positive shift (+8 mV) of the activation curve. Action potential simulation study was conducted based on the KYOTO model to estimate the influence of additional gene modifiers. In both models mimicking LQT1 plus 2 and LQT1 plus 7, the incidence of early afterdepolarization was increased compared with the LQT1 model under the setting of beta-adrenergic stimulation. CONCLUSION: Multiple mutations in different LQTS-related genes may modify clinical characteristics. Expanded gene survey may be required in LQT1 patients who are resistant to beta-blocker therapy.

Action Potentials↗
PubMed2004

Detection of metabolic abnormality in asynergic regions of ischemic human myocardium using 31P and 1H magnetic resonance spectroscopy.

To assess quantitatively phosphocreatine (PCr), adenosine triphosphate (ATP) and total creatine (CR) in asynergic regions of ischemic human myocardium using phosphorus (31P) and proton magnetic resonance spectroscopy (1H MRS). Patients were divided into two groups: 31P MRS and 1H MRS. In each group, patients were subdivided into three groups using echocardiography: a normokinetic [WN(P) (n = 6) in 31P MRS, WN(H) (n = 10) in 1H MRS], a hypokinetic [WH(P) (n = 13), WH(H) (n = 7)], and a- or dyskinetic wall motion groups [WA(P) (n = 14), WA(H) (n =6)]. They were compared with normal subjects of each group [CNP (n = 10), CN(H) (n = 10)]. 31P MRS spectra were obtained from the anterior and apical regions of the left ventricle by slice-selected 1D CSI. 1H MRS spectra were obtained from the 2 x 2 x 2-cm voxel set in the left ventricular wall by the PRESS method. In the 31P MRS group, myocardial PCr was significantly lower in the WH(P) and WA(P) groups than in the CN(P) group, but myocardial PCr in the WN(P) group did not differ from that in CN(P). A difference in ATP could not be detected among the four groups. In the 1H MRS group, myocardial CR was significantly lower in the WH(H) and WA(H) groups than in the CN(H) group. Myocardial CR in the WNH group did not differ from that in the CN(H). The noninvasive 31P and 1H MRS approach is useful in the assessment of metabolite reduction associated with wall motion abnormality.

Adenosine Triphosphate↗
PubMed2004

Bepridil block of recombinant human cardiac IKs current shows a time-dependent unblock.

Whole-cell patch-clamp techniques were employed to examine the effects of bepridil, a Ca2+ channel blocker with Vaughan Williams class III action, on a slow component of cardiac delayed rectifier K+ current (IKs), which was reconstituted in HEK293 cells by transfecting KCNQ1 and KCNE1. Micromolar bepridil inhibited tail currents carried by KCNQ1/KCNE1 channels in a concentration-dependent manner (IC50 = 5.3 +/- 0.7 microM at -40 mV from 1000 milliseconds test pulse). When the effect of the drug was examined with a short test pulse protocol (250 milliseconds), IC50 became two-fold smaller than that measured with 1000 milliseconds test pulse (2.5 +/- 0.8 microM). The envelope-of-tails protocol was used to assess how the duration of depolarizing pulse affects the drug action on the outward KCNQ1/KCNE1 channel current. The drug significantly inhibited tail currents more potently during shorter pulses (<600 milliseconds). Bepridil's block was therefore time dependent, and its binding affinity to the channel was greater in the closed state channel, as evidenced by unblocking during prolonged depolarization. These properties of channel blockade appear to underscore the mechanism of bepridil's effect on IKs current.

Bepridil↗
PubMed2004

The relationship between flow-mediated brachial artery vasodilation and coronary vasomotor responses to bradykinin: comparison with those to acetylcholine.

Flow-mediated dilation (FMD) of brachial artery provides a noninvasive assessment of coronary endothelial dysfunction. Acetylcholine (ACh) has been used as an agent for estimating coronary endothelial function. In contrast to ACh, there is no evidence for a relationship between FMD and coronary vasodilation to bradykinin (BK). The aim of this study was to compare the flow-mediated vasodilation of brachial artery with coronary vasomotor responses to intracoronary ACh or BK in patients with an angiographically normal left anterior descending coronary artery. Ninety-one patients underwent the cardiac catheterization examination with coronary endothelial function testing and the brachial ultrasound study. BK (0.2, 0.6, 2.0 microg/min) and ACh (3, 10, 30 microg/min) were administered into the left coronary artery in a stepwise manner. Coronary blood flow was evaluated by the Doppler flow velocity measurement. Coronary diameters were measured by the quantitative coronary angiography. The assessment of endothelial function in the brachial artery was made in response to reactive hyperemia with high-resolution ultrasound. Bradykinin induced dose-dependent increases in epicardial coronary diameter and blood flow. There was a significant positive correlation between FMD- and BK-induced vasodilations of epicardial coronary arteries (0.2 microg/min: r = 0.30; 0.6 microg/min: r = 0.42; 2.0 microg/min: r = 0.44, P < 0.01, respectively) and resistance coronary arteries (0.2 microg/min: r = 0.40; 0.6 microg/min: r = 0.56; 2.0 microg/min: r = 0.59, P < 0.0001, respectively). FMD correlated with ACh-induced vasomotions of resistance but not epicardial coronary arteries. No correlation was seen between nitroglycerin-induced brachial artery vasodilation and BK-induced coronary vasodilation. The endothelial dysfunction of peripheral arteries correlated well with that of the coronary arteries especially vasomotor responses to BK.

Acetylcholine↗
PubMed2004

Long-term treatment with a phosphodiesterase type 5 inhibitor improves pulmonary hypertension secondary to heart failure through enhancing the natriuretic peptides-cGMP pathway.

In advanced heart failure (HF), the compensatory pulmonary vasodilation is attenuated due to the relative insufficiency of cGMP despite increased secretion of natriuretic peptides (NPs). Phosphodiesterase type 5 (PDE5) inhibitors prevent cGMP degradation, and thus may potentiate the effect of the NPs-cGMP pathway. We orally administered a specific PDE5 inhibitor, T-1032 (1 mg/kg; twice a day, n = 7) or placebo (n = 7) for 2 weeks in dogs with HF induced by rapid pacing (270 bpm, 3 weeks) and examined the plasma levels of atrial natriuretic peptide (ANP), cGMP, and hemodynamic parameters. We also examined the hemodynamic changes after injection of a specific NPs receptor antagonist, HS-142-1 (3 mg/kg), under treatment with T-1032. T-1032 significantly increased plasma cGMP levels compared with the vehicle group despite low plasma ANP levels associated with improvement in cardiopulmonary hemodynamics. HS-142-1 significantly decreased plasma cGMP levels in both groups, whereas it did not change all hemodynamic parameters in the vehicle group. In contrast, in the T-1032 group, HS-142-1 significantly increased pulmonary arterial pressure and pulmonary vascular resistance. These results indicated that long-term treatment with a PDE5 inhibitor improved pulmonary hypertension secondary to HF and the NPs-cGMP pathway contributed to this therapeutic effect.

3',5'-Cyclic-GMP Phosphodiesterases↗