Alpha1-adrenergic receptor subtype mRNAs are differentially regulated by alpha1-adrenergic and other hypertrophic stimuli in cardiac myocytes in culture and in vivo. Repression of alpha1B and alpha1D but induction of alpha1C.

Salbutamol (albuterol) is a beta 2-selective adrenoceptor agonist which accounts for its pronounced bronchodilatory, cardiac, uterine and metabolic effects. During the intervening years since salbutamol was first reviewed in the Journal (1971), it has become extensively used in the treatment of reversible obstructive airways disease. Numerous studies in this disease (including severe acute, childhood and exercise-induced asthma) have confirmed the bronchodilatory efficacy of salbutamol, and it has been shown to be at least as effective as most of the currently available bronchodilators, if not more effective. The onset of maximum effect of salbutamol is dependent on the formulation used and the route by which it is administered. In most patients inhaled salbutamol is a first-line therapy, since it offers rapid bronchodilation, usually relieving bronchospasm within minutes. Although oral salbutamol has often proved to be less efficacious than the inhaled formulation, it still affords clinically significant bronchodilation, and it is particularly useful in those patients unable to coordinate the use of inhalers. Parenteral formulations of salbutamol are generally reserved for the treatment of severe attacks of bronchospasm and they are one of the treatments of choice in these life-threatening situations. Studies of the concomitant use of salbutamol and other agents such as anticholinergics, methylxanthines and beclomethasone dipropionate have usually shown a complementary response in the majority of patients, as might be expected from the different mechanisms of action of these groups of drugs. Salbutamol is generally well tolerated and any side effects observed are a predictable extension of its pharmacology. Since the frequency of side effects is dose related, and therefore dependent on the route of administration, it is not surprising that they are much more common following intravenous and oral rather than inhalation therapy. Tremor, tachycardia and hypokalaemia are the most frequently reported adverse effects. After nearly 20 years of use, salbutamol is well established as a 'first-choice' treatment in reversible obstructive airways disease. Indeed, throughout this time many new bronchodilatory agents have been studied but none have proved more effective. Clinical evaluation of salbutamol in the treatment of premature labour, hyperkalaemia and cardiac failure awaits further studies, although to date some encouraging results have been reported.

Salbutamol in the 1980s. A reappraisal of its clinical efficacy.

Effects of losartan, a nonpeptide angiotensin II receptor antagonist, on cardiac hypertrophy and the tissue angiotensin II content in spontaneously hypertensive rats.

Systemic hypertension is a common cause of congestive heart failure. However, left ventricular (LV) systolic function remains normal for many years in patients with mild or moderate hypertension. In this study, high-quality M-mode echocardiograms were recorded in 7 patients with borderline hypertension, 14 patients with mild hypertension and 15 normal persons. Measures of systolic and diastolic LV function and the degree of LV hypertrophy were studied with the assistance of a tablet digitizer and dedicated microcomputer. Average blood pressure was 125 +/- 10/77 +/- 7 mm Hg in normal subjects, 146 +/- 18/92 +/- 2 mm Hg in patients with borderline hypertension and 150 +/- 11/102 +/- 4 in patients with mild hypertension. Indexes of systolic LV function were similar in all 3 groups. The peak rate of early relaxation of the LV posterior wall was significantly decreased in the group of patients with mild hypertension (4.7 vs 6.6 sec-1, p less than 0.01). The mitral valve closure rate was 150 +/- 32 mm/s in normal subjects, 119 +/- 35 mm/s in patients with borderline hypertension and 106 +/- 26 mm/s (p less than 0.001) in patients with mild hypertension. Mild LV hypertrophy was present in 6 of 7 patients with borderline and 13 of 14 patients with mild hypertension. The degree of hypertrophy and the level of blood pressure correlated poorly.(ABSTRACT TRUNCATED AT 250 WORDS)

Echocardiographic assessment by computer-assisted analysis of diastolic left ventricular function and hypertrophy in borderline or mild systemic hypertension

Interleukin-1β Is a Negative Transcriptional Regulator of α1-Adrenergic Induced Gene Expression in Cultured Cardiac Myocytes

The relations between some pressure and humoral factors, and some echocardiographic indexes of left ventricular (LV) hypertrophy were studied in 64 patients with essential hypertension. Fifty-seven percent of these patients showed echocardiographic evidence of LV hypertrophy (LV mass > 215 g). Multivariate stepwise regression analysis showed that only mean blood pressure (BP) and circulating norepinephrine (NE) levels were significantly related to LV mass index in the group of patients with LV hypertrophy. However, mean BP was the only factor related to LV mass index in the subgroup of patients with LV hypertrophy and plasma NE within the normal laboratory range, whereas NE was the sole factor related to LV mass index in the subgroup with LV hypertrophy and abnormally elevated NE levels (greater than mean + 2 standard deviations of the normal laboratory range). Correlation of LV mass index vs NE was −0.35 (not significant) in the former group of patients and 0.89 (p

Plasma norepinephrine and left ventricular hypertrophy in systemic hypertension.

The relative chronotropic and inotropic activity of preferential β1- and β2- adrenoceptor Stimulation was investigated in seven healthy male subjects in a randomized within-subject, single-blind study. Two doses of β1selective agonist prenalterol (1 mg/hr or 2 mg/hr) and of β2-selective agonist salbutamol (300 µg/hr or 600 µg/hr) were infused intravenously in four separate sessions, with intervals of at least 48 hr between sessions. At each session cuff blood pressure and heart rate (HR) were measured and some hemodynamic information on the inotropic state were derived by echocardiography. Both prenalterol and salbutamol induced increases in HR, but tachycardia was greater after salbutamol, whereas the positive inotropic response to β-stimulation was greater after prenalterol. At comparable HR rises (prenalterol, from 66.0 ± 5.5 to 72.2 ± 4 bpm; salbutamol, from 64.6 ± 6 to 70.0 ± 7 bpm), inotropic response seemed to be greater after prenalterol than after salbutamol (systolic blood pressure [SBP]: 133.5 ± 8 and 120.7 ± 8 mm Hg; mean velocity of circumferential fiber shortening [Vcf]: 1.54 ± 0.13 and 1.31 ± 0.12 c/s; ejection fraction [EF]: 72.4% ± 5% and 69.5% ± 4%; stroke index: 47.4 ± 4 and 41.7 ± 3 ml/m2). In presence of a chronotropic effect (HR from 64.6 ± 6 to 70.0 ± 7 bpm), the low salbutamol dose did not induce any changes in the indices of inotropism (SBP: from 119.2 ± 6 to 120.7 ± 8 mm Hg; mean Vcf: from 1.28 ± 0.11 to 1.31 ± 0.12 e/s; EF: from 68.1% ± 5% to 69.5% ± 4%; stroke index: from 40.2 ± 3 to 41.7 ± 3 ml/m2. On prenalterol, HR increases were accompanied by changes in all the indices of inotropism. Results would appear consistent with animal data in suggesting some heterogeneity of cardiac β-adrenergic receptors. Inotropic response to β-stimulation would appear to be mediated mostly by β1- adrenoceptors, whereas β1- and perhaps β2- adrenoceptors share a mediating action on chronotropic response to cardiac β-adrenoceptor stimulation.



Clinical Pharmacology and Therapeutics (1984) 35, 776–781; doi:10.1038/clpt.1984.111

Mario Motolese

Papers

Plasma norepinephrine and left ventricular hypertrophy in systemic hypertension.

Noninvasive assessment of chronotropic and inotropic response to preferential beta-1 and beta-2 adrenoceptor stimulation.