Antihypertensive treatment and cardiovascular risk management in patients with the metabolic syndrome - Focus on SNS and insulin resistance

Essential hypertension is very frequently associated with an over-activity of the sympathetic nervous system (SNS) and a decrease in insulin sensitivity of skeletal muscle glucose uptake, even when glycaemic control is (still) normal. In hypertensive patients, two major functions of insulin are impaired: there is insulin resistance of peripheral glucose uptake (primarily skeletal muscle) and insulin resistance of insulin-stimulated vasodilation. This insulin resistance is very often associated with dyslipidaemia, obesity, hypertension and impaired glucose tolerance, a cluster termed the "metabolic syndrome or the insulin resistance syndrome". Meta-analyses of antihypertensive intervention studies indicate a less than expected reduction of coronary events ("the coronary paradox"), although blood pressure had been lowered. These findings suggest, that lowering blood pressure is not enough. Furthermore, retrospective and very recent prospective data showed a higher incidence of type 2 diabetes in subjects treated with beta-blocking agents. Thus, the metabolic side effects of the antihypertensive treatment need to receive more attention. In the metabolic syndrome, a reduction of SNS drive would seem to be specifically effective. However, many groups have shown that antihypertensive treatment with beta-blockers, decreases insulin sensitivity by various mechanisms. In contrast the centrally acting agent moxonidine, an imidazoline I1- receptor agonist, may be of interest in this context. It inhibits sympathetic outflow and causes vasodilation. Moxonidine treatment improved insulin sensitivity specifically in insulin-resistant, obese patients with mild hypertension. Animal studies indicate an improvement of insulin-stimulated glucose uptake into the skeletal muscle and an improvement of glucose tolerance. Therefore, the beneficial characteristics of these newer class of antihypertensive agents suggest, that moxonidine could be advantageous for hypertensive patients with insulin resistance or type 2 diabetes. However, long-term studies are needed to confirm these benefits. In the cardiovascular risk management, lowering blood pressure is just one cornerstone. Due to the known metabolic "side effects" the selection of the antihypertensive agent might be relevant for the long-term outcome.