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Taking into consideration the available data in 1998, we believe that short-acting calcium antagonists should no longer be used in hypertensive patients. The practice of using oral or sublingual nifedipine in hypertensive emergency or pseudoemergency should be abandoned because it can lead to serious side effects such as syncope, myocardial infarction, stroke and even death. However, the use of a low dose of the long-acting formulations seems to be safe and promising in patients with essential hypertension. In the Hypertension Optimal Treatment (HOT) trial a calcium-antagonist based combination therapy reduced blood pressure by over 20 mmHg in most of the nearly 19,000 patients. Cardiovascular mortality in this study was with 3.8 per 1000 patient years clearlylower as compared to 6.5 per 1000 patient years reported in previous intervention trials. A long-acting dihydropyridine calcium antagonist was used in 78% of these patients. Clearly the calcium antagonists controversy was helpful in alerting physicians to the fact that hypertension remains a surrogate endpoint and that not all drugs that reduce blood pressure will reduce morbidity and mortality to the same extent. What was completely unnecessary, however, was the inappropriate news media coverage to the calcium blocker controversy that led to panic and confusion among patients and frustration among physicians. In this context we should perhaps remember the first rule in the treatment of Sir George Pickering: "Never frighten your patients."

A decrease in the vascular compliance of the large elastic vessels (reduction of their "Windkessel" function) is of decisive importance for the pathogenesis and prognosis of cardiovascular complications such as arteriosclerosis, left ventricular hypertrophy and heart failure. The effect of the antihypertensive calcium antagonist isradipine on the "Windkessel" function of the aorta was measured in terms of the central haemodynamics in ten patients (eight men, two women; mean age 58 +/- 3 years) with essential hypertension (WHO stage I-II) before and 3 months after treatment. The mean arterial blood pressure was obtained invasively from the aortic arch, cardiac output or stroke volume being obtained by the indicator dilution method. The ratio stroke volume/blood pressure amplitude was calculated as a measure of vascular compliance. After 3 months of treatment with isradipine the mean arterial blood pressure fell from 114 +/- 4 to 97 +/- 3 mm Hg (P < 0.01), and total peripheral resistance from 22 +/- 1 to 18 +/- 1 U, P < 0.05), while vascular compliance rose from 1.07 +/- 0.10 to 1.58 +/- 0.10 ml/mm Hg, P < 0.05. The increase in compliance resulted from both the fall in blood pressure per se and the pressure-independent increase in the distensibility of the vessel wall (87 +/- 8% as against 107 +/- 13%, P < 0.05). As the fall in afterload favoured regression in left ventricular hypertrophy and heart failure, this pressure-independent structural and (or) functional change in the great elastic arteries could be decisive for the cardiovascular prognosis of hypertensives.

Left ventricular hypertrophy is a frequent and early manifestation of cardiac structural adaptation in patients with essential hypertension. Prospective studies have clearly demonstrated that left ventricular hypertrophy represents a risk factor for cardiovascular morbidity and mortality, including sudden cardiac death. The increased risk is independent of the impact of high blood pressure and other risk factors on the cardiovascular system. Various clinical studies noted increased prevalence and severity of premature ventricular beats in hypertensive patients with left ventricular hypertrophy. Hypertrophy of myocardial cells, dilation of the left ventricle, increased stress of subendocardial myocardium and impaired coronary reserve are discussed as a possible pathogenetic link between myocardial hypertrophy and ventricular arrhythmias. Therapeutically, the primary goal for ventricular arrhythmias in hypertensive patients with left ventricular hypertrophy is regression of left ventricular mass. For this purpose, centrally sympatholytic agents, angiotensin converting enzyme inhibitors, betablockers and calcium antagonists have been found to be effective. Recently we observed that a reduction of left ventricular hypertrophy was associated with a decreased prevalence and severity of ventricular arrhythmias. Nevertheless, prospective studies are required to demonstrate whether reduction of severe ventricular arrhythmias helps to prevent sudden cardiac death due to left ventricular hypertrophy in hypertension.

In a 52-year-old patient with Bartter's syndrome, peripheral venous prostaglandin E2 (PGE2) and plasma renin activity (PRA) levels were markedly elevated and plasma aldosterone concentration (pa) was at the upper limit of normal, though inappropriately high relative to the decreased plasma and whole body potassium levels. Blood pressure, plasma volume, exchangeable body sodium, plasma cortisol and urinary catecholamines were normal. Renal venous PGE2 was two to three times higher than peripheral PGE2. Indomethacin (300 mg/day) decreased peripheral PGE2 by 50%, PRA by 84% and PA by 72%, induced a positive potassium balance (greater than 350 mEq) with normal plasma potassium levels, and returned the previously marked resistance to the pressor effect of angiotensin II to normal. During the entire study, highly significant correlations (p less than 0.001) between peripheral PGE2 and PRA (r = 0.86) or PA (r = 0.90) were found. In this patient the hyperreninemia was not related to volume depletion. These data indicate that in Bartter's syndrome renal PGE2 secretion may be increased, systemic blood levels of PGE2 may be elevated and closely related to PRA, and indomethacin ameliorates these abnormalities and improves potassium balance. These results are consistent with the ascription of an important role to excessive renal PGE2 secretion in the pathogenesis of Bartter's syndrome.