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Biomedical subjects

R R Wenzel

Publications and source records attributed to R R Wenzel.

At least 37 records · Page 2Linked to original sources
PubMed1998

Accuracy of a new wrist cuff oscillometric blood pressure device: comparisons with intraarterial and mercury manometer measurements.

Accurate measurement of arterial blood pressure is of great importance for the diagnosis and treatment of hypertension. Because of the chronic nature of antihypertensive drug therapy, the involvement of the patient in blood pressure control is desirable. Such an involvement, however, is only feasible if simple, user-friendly, and precise blood pressure measurement devices are available. In this study we tested a new wrist cuff oscillometric blood pressure measurement device in 100 consecutive patients undergoing cardiac catheterization. Blood pressures were simultaneously taken intraarterially (axillary artery) and with a mercury manometer and stethoscope or noninvasive measurement device (OMRON R3). Intraarterial measurements were directly compared with two measurements taken in random order with either an arm cuff mercury manometer or the wrist cuff device. Systolic and diastolic blood pressure as assessed with the mercury manometer was higher, especially when compared with the intraarterial and the wrist cuff values, which were comparable. Correlations of blood pressure values with intraarterial measurement were 0.86 systolic and 0.75 diastolic (P < .01) for the wrist cuff and 0.84 systolic (P < .01) and 0.59 diastolic (P < .05) for the mercury manometer measurements. Reproducibility of both measurements was good for the wrist cuff device ([systolic/diastolic]: r = 0.94/0.92; P < .01) and the mercury manometer (r = 0.97/0.88; P < .01). Both methods overestimated high diastolic values, whereas only the wrist cuff underestimated high systolic values. Thus, the new oscillometric wrist cuff blood pressure measurement device measures arterial blood pressure with great accuracy and reproducibility. As compared with intraarterial values, the wrist cuff device overestimated high diastolic and underestimated high systolic blood pressure values. Blood pressure values as measured by the mercury manometer were higher than intraarterial values and those of the wrist cuff. Both noninvasive devices overestimated high diastolic values.

Blood Pressure Determination↗
PubMed1998

Endothelin-1 induces vasodilation in human skin by nociceptor fibres and release of nitric oxide.

AIMS: Endothelin is a peptide produced by endothelial cells with many biological properties. In the human skin microcirculation endothelin induces neurogenic vasodilation associated with burning pruritus. We investigated the mechanisms involved in this response. METHODS: The effects of prolonged pretreatment with capsaicin, a specific inhibitor of polimodal nociceptor fibres, and of the nitric oxide synthase inhibitor L-NMMA on endothelin-1-induced vasodilation were studied in 15 human subjects. Furthermore, we investigated the effects of the ET(A)-selective antagonist PD147953 on bradykinin-induced vasodilation. RESULTS: After local injection, endothelin-1 caused vasoconstriction at the injection site and a profound vasodilation in the surrounding area (flare reaction, P<0.01). This response was specific and not induced by saline, albumin, acetylcholine or an ET-antagonist. Prolonged capsaicin pretreatment inhibited endothelin-1 induced vasodilation in the area surrounding the injection site, but not the central vasoconstriction at the injection site. Bradykinin also induced a marked vasodilation in the area surrounding the injection site; this was not inhibited by an ETA-selective antagonist, while the flare reaction was. L-NMMA applied at the site of the flare reaction prevented endothelin-1-induced vasodilation. CONCLUSIONS: Endothelin-1 in the human skin microcirculation stimulates polimodal nociceptor fibres leading to the release of nitric oxide. This response may play a pathophysiological role in inflammatory processes in the human skin.

Adolescent↗
PubMed1998

I1-imidazoline agonist moxonidine decreases sympathetic nerve activity and blood pressure in hypertensives.

Moxonidine is an I1-imidazoline receptor agonist that reduces blood pressure in hypertensives. Experimental data suggest that moxonidine inhibits central sympathetic activity. However, whether such a mechanism is involved in vivo in humans is still unclear. We investigated the effects of 0.4 mg moxonidine orally on muscle sympathetic nerve activity and heart rate in an open study in 8 healthy volunteers. Furthermore, we studied the effects of 0.4 mg moxonidine on muscle sympathetic nerve activity, heart rate, blood pressure, 24-hour blood pressure profile, and hormone plasma levels in 25 untreated hypertensives in a double-blind, placebo-controlled study. Moxonidine decreased muscle sympathetic nerve activity in both healthy volunteers (P<0.05 versus baseline) and hypertensives (P<0.02 versus placebo). Plasma norepinephrine also decreased (P<0. 01), whereas plasma epinephrine and renin levels did not change (P=NS). Furthermore, moxonidine decreased systolic (P<0.0001) and diastolic (P<0.001) blood pressure. Heart rate decreased after moxonidine in healthy subjects (P<0.05); in hypertensives, heart rate decreased during the night hours (P<0.05) but not during daytime (P=NS). Plasma levels of LDL, HDL, and total cholesterol were not influenced by the drug (P=NS). Moxonidine decreases systolic and diastolic blood pressure by inhibiting central nervous sympathetic activity. This makes this new drug suitable for the treatment of human hypertension and possibly for other cardiovascular diseases with increased sympathetic nerve activity, ie, ischemic heart disease and heart failure.

Adult↗
PubMed1998

Calcium antagonists and sympathetic nerve activation: are there differences between classes?

ACTIONS OF THE SYMPATHETIC NERVOUS SYSTEM: The sympathetic nervous system is an important cardiovascular regulator, particularly during stress and exercise; its sympathetic nervous activity is regulated in centers in the brain stem and transmitted to organs and blood vessels that are innervated by sympathetic nerve endings. In the heart, the sympathetic nervous system increases heart rate and contractility. The effect of the sympathetic nervous system in different vascular beds depends on the degree of innervation, the distribution of postjunctional receptors and the effect of local mediators. Overactivation of the sympathetic nervous system may lead to hypertension and is involved in heart failure. The degree of sympathetic activation determines prognosis in heart failure. Hence, vasodilators ideally should also blunt sympathetic activity, or at least avoid activating it. DIFFERENCES AMONG CALCIUM ANTAGONISTS: Calcium antagonists are widely used for the treatment of hypertension and coronary artery disease. Their main mechanism of action is inhibition of L-type Ca2+ channels. Short-acting nifedipine leads to a marked increase in heart rate, sympathetic nerve activity and plasma catecholamines, similar to those induced by a cold pressor test. With long-acting nifedipine heart rate does not increase, but sympathetic nerve activity does increase. Other calcium antagonists have been less thoroughly investigated, but indirect evidence suggests differences between the different classes. Verapamil and diltiazem lower heart rate. Plasma noradrenalin measurements suggest that verapamil does not stimulate the sympathetic nervous system, but tends to suppress it. Second-generation dihydropyridines with longer duration of action do not increase heart rate; their effects on peripheral sympathetic nerve activity are not clear. Thus, in summary, the different classes of calcium antagonists differ with regard to their effects on sympathetic nerve activation. A decrease in heart rate and nerve activity might be beneficial for long-term prognosis, particularly in hypertension and heart failure.

Blood Circulation↗
PubMed1998

Role of sympathetic nervous system in hypertension and effects of cardiovascular drugs.

The sympathetic nervous system (SNS) plays an important role in the regulation of cardiac performance and peripheral circulation. Changes in SNS activity measured as catecholamines in plasma or organ spillover have been implicated in the pathogenesis of hypertension. Recent studies using microneurography to directly assess peripheral sympathetic nerve activity have demonstrated an increase in sympathetic activity in patients with borderline hypertension at rest and during hypoxia. We have recently shown that resting muscle sympathetic nerve activity is comparable in offspring of hypertensive and normotensive parents. However, during mental arithmetic the increase in muscle sympathetic nerve activity and blood pressure was significantly more pronounced in offspring of hypertensive than in offspring of normotensive parents, but resting blood pressure was in the normotensive range and comparable in both groups. These data indicate that the response to mental stress results in a more pronounced activation of SNS in normotensive subjects with a genetic background of hypertension. In other cardiovascular disease states such as acute myocardial infarction and heart failure activity of the SNS may determine prognosis significantly. Some calcium antagonists which are successfully used to treat patients with hypertension and stable angina pectoris may have unfavourable effects in patients with impaired left ventricular function. This could be due in part to baroreceptor-mediated activation of the SNS, an effect which seems to be related to pharmacokinetics and pharmacodynamics of the drugs. In contrast, angiotensin converting enzyme inhibitors seem to directly decrease sympathetic nerve activity. This may explain at least in part their beneficial effects in patients with impaired left ventricular function. Thus, the SNS as a regulator of the cardiovascular system also plays an important role in the pathophysiology of cardiovascular diseases such as hypertension, myocardial infarction and heart failure. Furthermore, drug therapy could have a significant impact on the activity of the SNS.

Arousal↗
PubMed1997

Differential effects of captopril and nitrates on muscle sympathetic nerve activity in volunteers.

BACKGROUND: The sympathetic nervous system (SNS) is an important regulator of cardiovascular function. Activation of SNS plays an important role in the pathophysiology and the prognosis of cardiovascular diseases such as heart failure, acute coronary syndromes, arrhythmia, and possibly hypertension. Vasodilators such as adenosine and sodium nitroprusside are known to activate SNS via baroreflex mechanisms. Because vasodilators are widely used in the treatment of patients with cardiovascular diseases, the aim of the present study was to assess the influence of clinically used dosages of isosorbide dinitrate and captopril on sympathetic nerve activity at rest and during stimulatory maneuvers. METHODS AND RESULTS: Twenty-eight healthy volunteers were included in this double-blind placebo-controlled study, and muscle sympathetic nerve activity (MSA; with microelectrodes in the peroneal nerve), blood pressure, heart rate, and neurohumoral parameters were measured before and 90 minutes after the oral administration of 40 mg isosorbide dinitrate or 6.25 mg captopril. Furthermore, a 3-minute mental stress test and a cold pressor test were performed before and 90 minutes after drug administration. Resting MSA did not change after captopril and decreased compared with placebo (P < .05 versus placebo), whereas isosorbide dinitrate led to a marked increase in MSA (P < .05). Systolic blood pressure was reduced by isosorbide dinitrate (P < .05), whereas captopril decreased diastolic blood pressure (P < .05). The increases in MSA, blood pressure, and heart rate during mental stress were comparable before and after drug administration regardless of the medication. During cold pressor test, MSA and systolic and diastolic blood pressures increased to the same degree independent of treatment, but after isosorbide dinitrate, the increase in MSA seemed to be less pronounced. Heart rate did not change during cold stimulation. Plasma renin activity increased after captopril and isosorbide dinitrate (P < .05), whereas placebo had no effect. Endothelin-1 increased after placebo and isosorbide dinitrate (P < .05) but not after captopril. CONCLUSIONS: Thus, captopril suppressed MSA despite lowering of diastolic blood pressure but allowed normal adaptation of the SNS during mental or physical stress. In contrast, the nitrate strongly activated the SNS under baseline conditions. These findings demonstrate that vasodilators differentially interact with the SNS, which could be of importance in therapeutic strategies for the treatment of patients with cardiovascular diseases.

Adult↗
PubMed1997

Differential activation of cardiac and peripheral sympathetic nervous system by nifedipine: role of pharmacokinetics.

OBJECTIVES: We sought to study the effects of short-acting and long-acting nifedipine on the sympathetic nervous system (SNS), heart rate (HR) and blood pressure (BP) of normotensive subjects under baseline conditions and during SNS stimulation. BACKGROUND: Calcium channel antagonists in different pharmacokinetic formulations are widely used in patients with coronary artery disease or hypertension. Short-acting formulations activate the SNS, an action that may be disadvantageous in patients with coronary disease, especially if left ventricular function is impaired. The effects of slow-release formulations on the SNS are unknown. METHODS: We used microneurography to investigate the influence of nifedipine (5 mg; 10 mg; and slow-release [GITS], 60 mg) on muscle sympathetic nerve activity (MSA) and skin sympathetic nerve activity (SSA) in healthy volunteers. RESULTS: Peak plasma levels after short-acting and slow-release nifedipine were achieved within 60 min and 330 min, respectively. Short-acting (10 mg, n = 10) and slow-release (n = 10) nifedipine, but not placebo, markedly activated MSA and increased plasma norepinephrine; plasma endothelin increased only with slow-release nifedipine. HR increased after short-acting nifedipine, but not after nifedipine GITS. Nifedipine had no effect on SSA (n = 6). Blockade of cardiac sympathetic activity (with esmolol) led to similar decreases in HR with or without nifedipine, whereas parasympatholysis (with atropine) led to similar increases in HR with or without nifedipine. The cold pressor test markedly increased MSA in all treatment groups and further increased MSA beyond the increase induced by nifedipine. CONCLUSIONS: Nifedipine markedly increased MSA, but not SSA, independently of drug release formulation. In contrast, HR increased with short-acting, but not with slow-release, nifedipine. Therefore, nifedipine activates cardiac and peripheral sympathetic nerves differently depending on pharmacokinetics. These effects of nifedipine may be disadvantageous in cardiac patients with increased sympathetic activity or congestive heart failure, or both.

Blood Pressure↗
PubMed1996

Endothelin and calcium antagonists in the skin microcirculation of patients with coronary artery disease.

BACKGROUND: Endothelin, a potent endothelium-derived vasoconstrictor peptide, is elevated in coronary artery disease (CAD); however, its pathophysiological role is uncertain. Calcium antagonists are widely used in patients with CAD. Using laser Doppler flowmetry, we investigated the influence of two endothelin antagonists and the calcium antagonist diltiazem on endogenous and exogenous endothelin in the skin microcirculation of CAD patients and healthy control subjects. METHODS AND RESULTS: Both endothelin antagonists and diltiazem applied intradermally induced vasodilation in CAD patients, which was more pronounced with the ETA/ETB antagonist than with the ETA antagonist or diltiazem. Exogenous endothelin led to profound vasoconstriction in CAD patients and healthy volunteers. Both endothelin antagonists and diltiazem blunted the vasoconstriction to exogenous endothelin in CAD patients and young healthy volunteers and less so in old healthy volunteers. However, compared with both endothelin antagonists, a 10-times-higher dose of diltiazem was required. Systemic diltiazem (240 mg, slow release) attenuated endothelin-induced vasoconstriction in CAD patients. Neurogenic vasodilation to exogenous endothelin was inhibited by both endothelin antagonists. CONCLUSIONS: This study demonstrates that endogenous endothelin of CAD patients contributes to the regulation of vascular tone in the skin microcirculation not only through ETA receptors but also possibly through ETB receptors. Diltiazem inhibited endothelin-induced vasoconstriction, but endothelin antagonists were slightly more effective. Thus, endothelin antagonists represent potent new tools to interfere with the vascular effects of endothelin in CAD patients. Future studies must confirm these findings in other areas of the circulation.

Administration, Oral↗
PubMed1996

Increased activation of sympathetic nervous system and endothelin by mental stress in normotensive offspring of hypertensive parents.

BACKGROUND: The pathogenesis of essential hypertension is still uncertain, but genetic factors and the sympathetic nervous system are likely to be involved. Sympathetic nerve activity and hormonal circulatory control mechanisms, however, are affected by blood pressure itself. Hence, early functional changes are best investigated in normotensive subjects at risk to develop hypertension, such as normotensive offspring of hypertensive parents. METHODS AND RESULTS: Muscle sympathetic nerve activity (MSA) was measured in the peroneal nerve of 10 normotensive offspring of parents with essential hypertension and 8 offspring of normotensive parents. Measurements were performed under resting conditions, during a 10-minute period of hypoxia (12.5% O2/87.5% N2) and during a 3-minute mental stress test. The tests were separated by a 30-minute resting period. Plasma samples for determination of norepinephrine and endothelin were collected before and after the tests. Baseline values of MSA were comparable in offspring of hypertensive and normotensive parents. During hypoxia, MSA, heart rate, and norepinephrine and endothelin plasma levels increased in offspring of hypertensive and normotensive parents to a comparable degree, whereas no significant changes in blood pressure and plasma norepinephrine levels were observed in either group. During mental stress, MSA and plasma norepinephrine and endothelin increased only in offspring of hypertensive parents (P < .001 to .01). In parallel, blood pressure increased significantly only in offspring of hypertensive parents (P < .001 to .05) but heart rate increased in both groups (P < .001 to .05). CONCLUSIONS: The activity of the sympathetic nervous system and plasma norepinephrine and endothelin levels are increased during mental stress only in offspring of hypertensive parents, whereas the response to hypoxia was similar in offspring of hypertensive and normotensive parents, suggesting a genetically determined abnormal regulation of the sympathetic nervous system to certain stressful stimuli in offspring of hypertensive parents. This may play a role in the pathogenesis of essential hypertension.

Adult↗
PubMed1996

[Sympathetic nervous system and endothelial function in heart failure].

Congestive heart failure is a frequent cardiovascular disease with a poor prognosis in advanced stages. Activation of neurohumoral systems such as the renin-angiotensin system and the sympathetic nervous system as well as impairment of local regulatory mechanisms (i.e. adrenoceptors, endothelial factors) play an important role in the pathogenesis and prognosis of the disease. The increase in peripheral resistance is due to imbalance of vasoconstrictors and vasodilators in favour of the vasoconstrictors and to changes in endothelial function, i.e. impaired production of nitric oxide, increased production of endothelin. Sodium and volume retention as well as the activation of the renin-angiotensin system increase preload. The sympathetic nervous system, which is known to be an independent negative prognostic factor, is activated and interacts with the renin-angiotensin system; however, up to now it is uncertain, whether these pathophysiological findings contribute to the development of congestive heart failure or if they are only secondary phenomena.

Amino Acid Sequence↗
PubMed1996

[Therapeutic measures following acute myocardial infarct: differential use of PTCA, surgery and drugs].

Myocardial infarction represents a crossroads in the natural history of coronary artery disease. The prognosis is determined by the severity of coronary artery disease, infarct size (and hence ejection fraction), and age of the patient. After infarction, patients may remain symptomless, or suffer angina, silent ischemia, reinfarction, heart failure or sudden death. Hence patient management after infarction includes (1) estimation of risk, (2) the use of stress tests to detect ischemia and rhythm disorders, (3) PTCA or bypass if required and (4) medical therapy. Cardiac catheterization is indicated in patients with angina or silent ischemia, non-Q wave infarction or large infarctus; its use is less well established in patients without ischemia and left ventricular dysfunction, but this indication is nevertheless increasingly accepted. PTCA is primarily utilized in patients with single or two vessel disease, while coronary bypass surgery is indicated in patients with left main or three vessel disease. All these measures are designed to improve symptoms and prognosis. For secondary prevention medical therapy should be used to treat cardiovascular risk factors (antihypertensive drugs, lipid-lowering drugs etc.), to inhibit platelets (aspirin, ticlopidine) or coagulation (coumarins), to block neurohumoral activation (betablocker, ACE-inhibitors), for vasoconstriction (calcium channel blockers, nitrates) and to suppress arrhythmias. The large number of drugs requires reasoned use depending on the risk profile of the individual patient. Cardiovascular risk factors should be treated appropriately. Platelet inhibitors should be given to all patients except those with atrial fibrillation or large ventricles (coumarins). Betablockers reduce mortality, reinfarction and sudden death after infarction and hence should be used if no contraindications exist. ACE-inhibitors are particularly effective in improving symptoms and prognosis in patients with impaired left ventricular function. Calcium antagonists should be used with caution and only in patients with normal left ventricular function. Nitrates are primarily effective in improving symptoms in patients with angina or heart failure. Antiarrhythmic drugs (amiodarone) are only useful in patients with complex arrhythmias. Digitalis has been shown to improve symptoms in patients with heart failure, while other inotropic drugs are virtually no longer used. These guidelines allow reasoned differential therapy after myocardial infarction to the maximum benefit of the patient and at minimum cost.

Adrenergic beta-Antagonists↗
PubMed1995

[Mechanisms of acute coronary syndrome].

The pathogenesis of coronary artery disease is characterized by an increased vasoconstriction, activation of platelet vessel wall interactions as well as the invasion of monocytes into the subintima with deposition of lipids as well as proliferation and migration of vascular smooth muscle cells. In the acute coronary syndromes plaque rupture as well as activation of platelets and coagulation as well as coronary vasoconstriction play an important role. Clinically these mechanisms lead to unstable angina and myocardial infarction. For the understanding of acute coronary syndromes, the mechanisms operative in the healthy blood vessel wall are important. Healthy coronary arteries are in a constant state of vasodilatation, platelets as well as the coagulation cascade are inactivated and vascular smooth muscle cells of the media are quiescent. Endothelial mediators such as nitric oxide, prostacyclin and tissue plasminogen activators and other mediators play an important role in this regard. The continuous release of nitric oxide and prostacyclin keeps the coronary circulation in a state of vasodilatation and inhibits platelet vessel wall interaction. Other mediators of the endothelium also inhibit coagulation and migration and proliferation of vascular smooth muscle cells. On the other hand in patients with cardiovascular risk factors and possibly also in those with genetic disposition as well as with aging, these mechanisms are impaired and in turn increased vasoconstrictor responses of coronary arteries, activation of platelet vessel wall interaction, invasion of monocytes into the subintima with lipid storage and proliferation/-migration of vascular smooth muscle cells occur. A cause oriented therapy of coronary artery disease and of acute coronary syndromes in particular must be based on these pathophysiological mechanisms.

Acute Disease↗
PubMed1995

Endothelin and endothelin antagonists: pharmacology and clinical implications.

Endothelins (ET) are a family of peptides with potent biological properties. Endothelial cells produce exclusively ET-1 while other tissues produce ET-2 and ET-3. The production of ET requires an increase in intracellular Ca2+. This increase can be induced by physical chemicals (i.e. hypoxia) or receptor-operated stimuli (i.e. thrombin, angiotensin II, arginine vasopressin, transforming growth factor beta 1, interleukin-1). Most of ET is released abluminally towards vascular smooth muscle and less luminally. The main vascular effect of ET are vasodilation (transient), profound and sustained vasoconstriction as well as proliferation of vascular smooth muscle. These biological effects are mediated by distinct receptors. Three ET receptors have been cloned, i.e. ETA-, ETB- and ETC-receptors. In vascular tissue ETA-receptors are expressed on vascular smooth muscle and responsible for vasoconstriction. ETB-receptors are expressed on endothelium and linked to nitric oxide and/or prostacyclin release. Activation of these receptors explains the transient vasodilation with intraluminal application of ET. Vascular smooth muscle cells can express ETB-receptors which contribute to ET-induced vasoconstriction particularly at lower concentrations. The role of the recently cloned ETC-receptor in the vasculature is still uncertain. ET production is increased (as judged from circulating plasma levels) in vascular disease and atherosclerosis in particular, in myocardial infarction and heart failure, pulmonary hypertension and renal disease. ET production is increased in arterial hypertension remains controversial. Non-peptidic ET antagonists have been developed which either block ETA- receptors or ETA- and ETB-receptors simultaneously. The advantage of ETA-receptors is that they leave the endothelium-dependent vasodilation to ET (via ETB-receptor) intact. However, ETB-mediated contraction remains unaffected by these antagonists. In contrast ETA-/ETB-antagonists fully prevent ET-induced vasoconstriction, however, they also inhibit the endothelial effects of the peptide. ET antagonists interfere with the effects of ET in isolated vascular tissue (including that obtained from humans) as well as in vivo. In humans, ETA as well as ETA-/ETB-antagonists inhibit endothelin-induced vasoconstriction. Hence in summary ET are a family of potent peptides with profound effects in the vasculature. Several studies suggest a role of ET in cardiovascular disease. The newly developed ET-antagonists are potent and selective tools to delineate the (patho-)physiological roles of ET and may become a new class of cardiovascular drugs.

Amino Acid Sequence↗
PubMed1995

Vascular protective effects of ACE inhibitors and calcium antagonists: theoretical basis for a combination therapy in hypertension and other cardiovascular diseases.

Hypertension is an important cardiovascular risk factor. High blood pressure per se is not a disease but a hemodynamic alteration associated with vascular disease. Two classes of drugs are especially effective in lowering blood pressure and preventing cardiovascular complications, angiotensin converting enzyme (ACE) inhibitors and calcium antagonists. The hemodynamic effects of ACE inhibitors and calcium antagonists are complementary. While ACE inhibitors inhibit the renin-angiotensin system and reduce sympathetic outflow, calcium antagonists dilate large conduit and resistance arteries. Certain calcium antagonists, such as verapamil, lower heart rate. In the blood vessel wall, the local vascular effects of ACE inhibitors and calcium antagonists are also complementary. While ACE inhibitors inhibit activation of angiotensin I into angiotensin II and prevent the breakdown of bradykinin (which stimulates nitric oxide and prostacyclin formation), calcium antagonists inhibit the effects of vasoconstrictor hormones such as angiotensin II at the level of vascular smooth muscle by reducing calcium inflow and facilitating the vasodilator effects of nitric oxide. Calcium antagonists reduce smooth muscle cell proliferation and atherosclerosis. In hypertensive animals, verapamil and trandolapril normalize endothelial dysfunction. In large angiographic trials, nifedipine and nicardipine reduced the development of new atherosclerotic plaques. After myocardial infarction, verapamil reduces mortality and cardiac events in patients without heart failure. In contrast, ACE inhibitors are effective after myocardial infarction in patients with impaired left ventricular function. Urinary albumin excretion rate decreases during ACE inhibitor therapy or with a calcium antagonist such as verapamil; combination of the two drugs has an additive effect. In resistance arteries, hypertension is associated with an increased media/lumen ratio. ACE inhibitors, but not beta-blockers, markedly improve these structural changes. In summary, ACE inhibitors and calcium antagonists have a complementary profile, both in their hemodynamic and local vascular action. Hence, combination therapy with these two classes of drugs appears particularly useful in patients with hypertension, not only to lower blood pressure, but hopefully to achieve improved cardiovascular protection.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Local regulation of the coronary circulation in health and disease: role of nitric oxide and endothelin.

Coronary artery disease is the leading cause of morbidity and mortality in western countries. Its pathogenesis is unknown, but involves enhanced vasoconstriction, increased interaction of platelets and monocytes with the vessel wall, as well as proliferation, migration and extracellular matrix formation of vascular smooth muscle. The endothelium lies in a strategic anatomical position between circulating blood and vascular smooth muscle cells. This supports the concept that dysfunction of these cells significantly contributes to coronary artery disease. Besides other mediators, endothelial cells are a source of nitric oxide and endothelin. Nitric oxide is a vasodilator, an inhibitor of both platelet function and proliferation and migration of vascular smooth muscle. Endothelin is a potent vasoconstrictor that facilitates proliferation. Under pathological conditions, in particular the presence of cardiovascular risk factors, endothelial dysfunction occurs and is a major contributor to the increase in platelet vessel wall interaction, vasoconstriction and proliferation in the coronary system. Endothelium-dependent vasodilation is usually reduced and endothelium-dependent constrictor responses, as well as endothelin production, are augmented. Hence, endothelial cells are important targets and mediators of coronary artery disease.

Animals↗