Sara Del Colle

Antihypertensive drugs and the sympathetic nervous system.

Hypertension has been associated with several modifications in the function and regulation of the sympathetic nervous system (SNS). Although it is unclear whether this dysfunction is primary or secondary to the development of hypertension, these alterations are considered to play an important role in the evolution, maintenance, and development of hypertension and its target organ damage. Several pharmacological antihypertensive classes are currently available. The main drugs that have been clearly shown to affect SNS function are β-blockers, α-blockers, and centrally acting drugs. On the contrary, the effects of ACE inhibitors (ACE-Is), AT1 receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics on SNS function remain controversial. These properties are pharmacologically and pathophysiologically relevant and should be considered in the choice of antihypertensive treatments and combination therapies in order to achieve, beyond optimal blood pressure control, a normalization of SNS physiology and the most effective prevention of target organ damage.

Baroreflex sensitivity correlates with left ventricular morphology and diastolic function in essential hypertension

Objectives Arterial hypertension is a common cause of cardiac organ damage, inducing morphological and functional modifications. Spontaneous baroreflex sensitivity (BRS) control of the heart rate is a key mechanism of blood pressure homeostasis, and is impaired in patients with hypertension. This study sought to assess the association between BRS and left ventricular morphology and function. Methods We studied 224 hypertensive patients (125 men; aged 47.8 ± 10.8 years, mean ± SD) compared with 51 normotensive control subjects (25 men, aged 45.7 ± 12.5 years). Left ventricular morphology, systolic and diastolic function were evaluated by echocardiography. Spontaneous BRS was measured using the sequence method. Results BRS was inversely associated with relative wall thickness (R2 = 0.17; P < 0.0001) and left ventricular mass index (R2 = 0.03; P = 0.01); in particular, BRS was significantly impaired in patients with concentric left ventricular remodelling (median [interquartile difference] 9.4 [4.1]) and hypertrophy (9.05 [3.9]) compared with the normal left ventricle (12.3 [5]; P < 0.001). BRS showed a significant association with systolic function evaluated by midwall fractional shortening (r = 0.28; P < 0.001), stroke volume (r = 0.27; P < 0.001), stroke work (r = 0.17; P < 0.05), and fractional shortening (r = 0.17; P < 0.05). BRS was significantly decreased in patients with diastolic dysfunction; it was lower in patients with diastolic dysfunction compared with both the control group and hypertensive patients with normal diastolic function. Conclusion BRS is associated with left ventricular morphology, systolic and diastolic function in hypertensive patients. In particular BRS is impaired in patients with diastolic dysfunction. These findings suggest a role for BRS as a target in arterial hypertension.

Heart Rate Variability and Baroreflex Sensitivity during Fosinopril, Irbesartan and Atenolol Therapy in Hypertension

ObjectiveTo evaluate the effects of long-term therapy with fosinopril, irbesartan and atenolol on the autonomic control of the cardiovascular system in hypertensive patients.MethodsWe enrolled 58 patients (mean age 38 ± 10 years) with never-treated mild hypertension with no evidence of target organ damage. The study was single blind. Patients were assigned to receive fosinopril 10–20 mg/day, irbesartan 150–300 mg/day or atenolol 50–100 mg/day for 14 weeks. Dosage was titrated to reach an average office blood pressure (BP) of <140/90mm Hg. Before therapy all patients underwent a 24-hour Holter ECG to evaluate heart rate variability (HRV) through nonlinear methods, 24-hour ambulatory BP monitoring (ABPM), and measurement of baroreflex sensitivity (BRS) using a Portaprés device; all measurements were repeated after therapy.ResultsAll three therapies significantly and equally decreased BP, both office (systolic/diastolic blood pressure 152 ± 11/97 ± 7mm Hg vs 129 ± 7/85 ± 4mm Hg after fosinopril, 151 ± 11/97 ± 6mm Hg vs 133 ± 9/87 ± 8mm Hg after irbesartan, 149 ± 13/96 ± 9mm Hg vs 132 ± 9/87 ± 7mm Hg after atenolol; p < 0.001) and ABPM values. HRV calculated with nonlinear methods and BRS were significantly increased after atenolol whereas no significant change was found in the fosinopril and irbesartan treatment groups.ConclusionsAll three therapies significantly and similarly reduced BP without modifying heart rate, except for atenolol, which significantly decreased it. Although angiotensin directly increases sympathetic tone, neither fosinopril nor irbesartan modified cardiovascular autonomic function; this is likely to be connected to the fairly good basal autonomic function of the population evaluated. Atenolol is associated with a significant increase in HRV and BRS probably through an improvement of parasympathetic tone.

Treatment of Patients with Neurogenic Orthostatic Hypotension

Neurogenic orthostatic hypotension (OH) is caused by disorders of the autonomic nervous system, and these disorders are classified as either primary (mainly multiple system atrophy, pure autonomic failure, and autonomic failure associated with Parkinson’s disease) or secondary (central nervous system diseases, peripheral neuropathies and systemic diseases). The effects of OH are often debilitating, in many cases confining the patient to bed. Moreover, longitudinal studies have shown that OH increases the risk of stroke, myocardial ischaemia and mortality.Treatment of patients with OH is aimed at reducing the postural symptoms. Nonpharmacological measures represent the first step in therapy, of which fluid repletion and physical counter manoeuvres have proven very effective.The pharmacological management of patients with OH can be problematic, and the possibility of developing supine hypertension and subsequent congestive heart failure should be kept in mind, especially in those patients with a pre-existing cardiovascular risk, such as diabetes mellitus or ischaemic heart disease.Randomised and controlled studies for the treatment of OH are still scarce and limited to a few agents and groups of patients. The drugs currently used are fludrocortisone, midodrine and dihydroergotamine. Fludrocortisone expands the extravascular body fluid volume and improves α-adrenergic sensitivity. Midodrine is a peripheral, selective α1-adrenergic agonist that causes arterial and venous vasoconstriction. Dihydroergotamine is an α1-adrenergic agonist with a selective venous vasoconstriction effect. In anaemic patients, erythropoietin has proven beneficial; postprandial hypotension responds to octreotide, which also improves orthostatic tolerance and does not cause supine hypertension.This review will discuss the therapeutic strategies for treating patients with symptomatic neurogenic OH.

Drug effects on aldosterone/plasma renin activity ratio in primary aldosteronism

Abstract—Primary aldosteronism is a specifically treatable and potentially curable form of secondary hypertension. The aldosterone/plasma renin activity ratio (ARR) is routinely used as a screening test. Antihypertensive therapy can interfere with the interpretation of this parameter, but a correct washout period can be potentially harmful. We have investigated the effects of therapy with atenolol, amlodipine, doxazosin, fosinopril, and irbesartan on the ARR in a group of 230 patients with suspected primary aldosteronism. The percent change from control of ARR in patients taking amlodipine was −17%±32; atenolol, 62%±82; doxazosin, −5%±26; fosinopril, −30%±24; and irbesartan, −43%±27. The ARR change induced by atenolol was significantly higher compared with that induced by all other drugs (P <0.0001), and the ARR change induced by irbesartan was significantly lower than that induced by doxazosin (P <0.0001). One of 55 patients from the group taking amlodipine (1.8%) and 4/17 of the patients taking irbesartan (23.5%) gave a false-negative ARR (<50). None of the patients of the groups taking fosinopril, doxazosin, and atenolol displayed a false-negative ARR. Doxazosin and fosinopril can be used in hypertensive patients who need to undergo aldosterone and PRA measurement for the diagnosis of primary aldosteronism; amlodipine gave a very small percentage of false-negative diagnoses. &bgr;-Blockers also do not interfere with the diagnosis of primary aldosteronism, but they can be responsible for an increased rate of false-positive ARRs. The high rate of false-negative diagnoses in patients undergoing irbesartan treatment requires confirmation in a higher number of patients.