Adequate therapy of essential primary hypertension remains a great challenge. One of the key issues is seen in a low patient compliance which results on a long-term in a mulitude of organ injuries. Also the concept that blood pressure reduction should be the main therapeutic target has become a controversial issue. The question remains whether underlying causes are treated to the same extent as a high blood pressure. It is conceivable that inadequately treated underlying causes have long-term detrimental actions which might, however, be more difficult to assess as compared to hypertension.
It remains an intriguing observation that the incidence of hypertension increases in Westernized societies with age but not in primitive societies. It is thought that a high caloric intake, high sodium intake, sedentary life-style and psychosocial stress have an important role in the manifestation of hypertension. It can also be concluded that in addition to genetic factors environmental influences must have a predominant influence. The majority of hypertensive strategies of the last years were, however, not targeted at molecular events associated with unfavorable life-style factors.
The present volume is focussed on one of the key life-style factors for hypertension, i.e. caloric intake. The contribution by leading experts in this field demonstrate that diet intake is a potent factor modulating sympathetic nervous system activity. It is not only shown that hypercaloric nutrition or the associated increase in body weight are linked with an increased sympathetic activity. It was initially intriguing that food restriction of normal weight animals is associated also with increased blood levels of catecholamines suggesting that a restricted food intake has effects generally interpreted as a stress response. It has become evident that more research is needed for defining the time-course of diet-based hypertension. It appears that initially a hyperkinetic hypertension evolves associated with high blood pressure and increased heart rates as a response to an increased caloric intake. If the underlying high sympathetic outflow is not treated adequately, secondary reactions arise leading to a gradual decrease in cardiac output and an increased peripheral vasoconstriction. It should also be taken into account that a hypercaloric nutrition represents an anabolic state associated with increased blood insulin levels. The combination of an increased sympathetic outflow of the brain and raised insulin levels are expected to favor the long-term manifestation of hypertension. In this respect it should be mentioned that an increased caloric intake in Westernized societies is associated with an increased sodium intake. Furthermore, an increased sodium intake has been shown to stimulate the sympathetic outflow of the brain. Taken together, an early event associated with common nutritional disorders of Westernized countries is linked to an increased sympathetic outflow of the brain.
Until recently, reducing the sympathetic outflow of the brain by drugs was associated with side effects which limited their general use. A key feature of these drugs is related to alpha adrenergic receptors which mediate not only a blood pressure rebound after drug withdrawal but also such phenomena as sedation which lead to a low patient compliance. The discovery of imidazoline receptors in the rostral ventrolateral medulla has opened novel avenues in the regulation of sympathetic outflow. There is increasing evidence that the rostral ventrolateral medulla represents the last efficient possibility in the brain for downregulating sympathetic outflow. The rostral ventrolateral imidazoline receptors have thus a key role in integrating influences which arise not only from diet intake but also from psychosocial stress and sodium intake. The present volume deals thus also with key features of moxonidine which prescribed as an antihypertensive drug with the highest selectivity for imidazoline receptors. It is also shown that moxonidine differs in crucial aspects from clonidine which binds to both imidazoline as well as alpha-adrenergic receptors. This therapeutic intervention is considered to represent an early intervention for reducing the incidence of catecholamine-linked damage which is referred to Excess Catecholamine Syndrome.
The novel drug approach is documented also in the logo of the symposium which depicts a brain with a normal and an excessive sympathetic outflow. The point where the excessive sympathetic outflow can be regulated is the medulla and it is considered important to re-establish a normal sympathetic outflow by drug interventions which selectively modulate the activity of imidazoline receptors of the medulla.
Heinz Rupp, Ph.D.
Editorial to the Symposium "The Excess Catecholamine Syndrome. From Cause to Therapy"
