The effect of sildenafil on human vascular function, platelet activation, and myocardial ischemia.

Objective: We studied the effects of sildenafil, a phosphodiesterase 5 inhibitor, on coronary and peripheral vascular function, platelet activation, and myocardial ischemia.

Background: Nitric oxide vasodilates and inhibits platelet activation by generating cyclic guanosine 5'-monophosphate, which is metabolized by phosphodiesterase type 5.

Methods: The effect of oral sildenafil on resting coronary vascular tone, endothelium-dependent and -independent function and platelet activation was measured in 24 patients.

Prognostic value of coronary vascular endothelial dysfunction.

Background: Whether patients at increased risk can be identified from a relatively low-risk population by coronary vascular function testing remains unknown. We investigated the relationship between coronary endothelial function and the occurrence of acute unpredictable cardiovascular events (cardiovascular death, myocardial infarction, stroke, and unstable angina) in patients with and without coronary atherosclerosis (CAD).

Methods And Results: We measured the change in coronary vascular resistance (DeltaCVR) and epicardial diameter with intracoronary acetylcholine (ACh, 15 micro g/min) to test endothelium-dependent function and sodium nitroprusside (20 micro g/min) and adenosine (2.

Anti-ischemic effects of angiotensin- converting enzyme inhibition in hypertension.

Objectives: We investigated whether augmentation of bradykinin (BK) bioavailability with angiotensin-converting enzyme (ACE) inhibition is associated with reduced exercise-induced myocardial ischemia in hypertension.

Background: Bradykinin responses are depressed in hypertension, and endothelial dysfunction contributes to myocardial ischemia by promoting abnormal coronary vasomotion during stress.

Methods: Fourteen hypertensive (HT) and 17 normotensive (NT), mildly symptomatic patients with coronary artery disease (CAD) and ST-segment depression during exercise were studied before and after seven days of oral enalapril (EN), which was titrated from 2.

Role of angiotensin II type 1 receptor in the regulation of cellular adhesion molecules in atherosclerosis.

Background: Inflammation is a central feature of coronary artery disease (CAD) that is characterized by increased expression of cellular adhesion molecules with the exception of L-selectin. L-selectin is a leukocyte adhesion molecule that is rapidly shed after leukocyte activation so that it appears to be decreased in CAD. The renin-angiotensin system (RAS) is implicated in atherogenesis and up-regulates these molecules.

Characterization of endothelium-derived hyperpolarizing factor in the human forearm microcirculation.

The identity of endothelium-dependent hyperpolarizing factor (EDHF) in the human circulation remains controversial. We investigated whether EDHF contributes to endothelium-dependent vasomotion in the forearm microvasculature by studying the effect of K+ and miconazole, an inhibitor of cytochrome P-450, on the response to bradykinin in healthy human subjects. Study drugs were infused intra-arterially, and forearm blood flow was measured using strain-gauge plethysmography.

Contribution of bradykinin receptor dysfunction to abnormal coronary vasomotion in humans.

Objectives: The aim of our study was to investigate coronary vascular kinin receptor function in patients with atherosclerosis or its risk factors.

Background: Although acetylcholine (ACH) is used as a probe for testing vascular function in vivo, endogenous bradykinin (BK) regulates resting and flow-mediated epicardial tone.

Methods: In 53 patients with mild atherosclerosis or its risk factors and 9 control subjects, endothelium-dependent vasomotion was tested with intracoronary ACH (30 microg/min) and BK (62.

Acute and chronic angiotensin-1 receptor antagonism reverses endothelial dysfunction in atherosclerosis.

Background: The renin-angiotensin system may contribute to atherogenesis through the promotion of endothelial dysfunction. The present study was performed to determine whether angiotensin-1 (AT(1)) receptor inhibition improves endothelial dysfunction.

Methods And Results: In the femoral circulation of 19 patients with atherosclerosis and of 9 control subjects, we studied microvascular responses to reactive hyperemia, angiotensin II, acetylcholine, and sodium nitroprusside before and after the administration of intra-arterial losartan (10 mg).

Oral L-arginine in patients with coronary artery disease on medical management.

Background: Vascular nitric oxide (NO) bioavailability is reduced in patients with coronary artery disease (CAD). We investigated whether oral L-arginine, the substrate for NO synthesis, improves homeostatic functions of the vascular endothelium in patients maintained on appropriate medical therapy and thus might be useful as adjunctive therapy.

Methods And Results: Thirty CAD patients (29 men; age, 67+/-8 years) on appropriate medical management were randomly assigned to L-arginine (9 g) or placebo daily for 1 month, with crossover to the alternate therapy after 1 month off therapy, in a double-blind study.

Effects of oral L-arginine on endothelium-dependent vasodilation and markers of inflammation in healthy postmenopausal women.

Objectives: We examined whether oral administration of L-arginine, the substrate for nitric oxide (NO) synthesis, increases NO bioactivity in healthy postmenopausal women.

Background: Nitric oxide may protect arteries against atherosclerosis, as suggested by experimental studies in animals. Estrogen therapy, which has been shown to increase NO bioactivity in the vasculature of healthy postmenopausal women, is not acceptable for long-term use by many women.

Vascular effects of estrogen and vitamin E therapies in postmenopausal women.

Background: Estrogen and vitamin E therapies have been suggested to reduce cardiovascular risk, but comparison of the vascular effects of these therapies to determine mechanisms of potential benefit has not been performed in postmenopausal women.

Methods And Results: In a double-blind, 3-period crossover study, we randomly assigned 28 healthy postmenopausal women to conjugated equine estrogens (CE) 0. 625 mg/d, vitamin E 800 IU/d, and their combination, with measurements made before and after each 6-week treatment period.

Relationship of the C242T p22phox gene polymorphism to angiographic coronary artery disease and endothelial function.

Patients with coronary artery disease (CAD) have impaired endothelial function in part due to an increase in vascular oxidant stress. p22phox, an essential component of the NADPH oxidase, is thought to play a critical role in the generation of superoxide anions in the vessel wall. The C242T polymorphism, located in the potential heme-binding site of the p22phox gene, has recently been reported to confer a protective effect on CAD risk in a Japanese study population.

Effects of hormone therapy on inflammatory cell adhesion molecules in postmenopausal healthy women.

To investigate the effect of estrogen with antioxidant potential on soluble markers of chronic vascular inflammation, we administered either transdermal 17beta-estradiol 0.1 mg/day (9 women) or 17beta-estradiol 0.1 mg and medroxyprogesterone acetate 2.

Effects of hormone-replacement therapy on fibrinolysis in postmenopausal women.

Background: Plasma levels of plasminogen-activator inhibitor type 1 (PAI-1), an essential inhibitor of fibrinolysis in humans, increase in women after menopause, and this may contribute to the risk of cardiovascular disease. We studied the effects of hormone-replacement therapy on PAI-1 levels.

Methods: In a randomized, crossover study, we investigated the effects of oral conjugated estrogen (0.

Imipramine in patients with chest pain despite normal coronary angiograms.

Background: Ten to 30 percent of patients undergoing cardiac catheterization because of chest pain are found to have normal coronary angiograms. Because these patients may have a visceral pain syndrome unrelated to myocardial ischemia, we investigated whether drugs that are useful in chronic pain syndromes might also be beneficial in such patients.

Methods: Sixty consecutive patients underwent cardiac, esophageal, psychiatric, and pain-sensitivity testing and then participated in a randomized, double-blind, placebo-controlled three-week trial of clonidine at a dose of 0.

Three year anatomic, functional and clinical follow-up after successful percutaneous transluminal coronary angioplasty.

Because the long-term anatomic effects of percutaneous transluminal coronary angioplasty are unknown, follow-up evaluations including coronary angiography, treadmill exercise testing and rest and bicycle exercise radionuclide angiography were performed in 46 patients 6.3 +/- 2.0 and 37.

Exercise, electrocardiographic and functional responses after percutaneous transluminal coronary angioplasty.

Exercise testing after successful PTCA showed improved cardiac functional status on examination of electrocardiographic and symptomatic responses, myocardial perfusion and global and regional left ventricular function. Sixty-six patients were studied before and after persistently successful PTCA. Follow-up studies an average of 8 months after the successful procedure showed an incidence of abnormal testing of only 7% using both electrocardiographic and subjective symptomatic criteria during treadmill studies and no abnormal studies with thallium scintigraphy.