Nervous system, resistance mechanism

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

The regulation of the total peripheral resistance also involves the complex interactions of several mechanisms. These include baroreflexes and sympathetic nervous system activity response to neurohumoral substances and endothelial factors myogenic adjustments at the cellular level, some mediated by ion channels and events at the cellular membrane and intercellular events mediated by receptors and mechanisms for signal transduction. As examples of some of these mechanisms, there are two major neural reflex arcs (Fig. 1). Baroreflexes are derived from high-pressure barorecep-tors in the aortic arch and carotid sinus and low-pressure cardiopulmonary baroreceptors in ventricles and atria. These receptors respond to stretch (high pressure) or... 

Overactivation of the sympathetic nervous system (SNS) may also play a role in the development and maintenance of primary hypertension for some individuals. Among other effects, direct activation of the SNS may lead to enhanced sodium retention, insulin resistance, and baroreceptor dysfunction.9 Regardless of which mechanism(s) underlie the role the SNS may play in the development of primary hypertension, the SNS remains a target of many antihypertensive agents. 

B-cell deficient mice are resistant to intraperitoneal inoculation with prions probably because of their involvement with FDC maturation and maintenance. The interface between FDCs and sympathetic nerves represents a critical site for the transfer of lymphoid prions into the nervous system however, the mechanism by which this is achieved remains unknown. Distinct forms of prion disease show differences in lymphoreticular involvement that may be related to the etiology of the disease or to divergent properties of distinct prion strains. For a review of prion disease peripheral pathogenesis see [18]. 

The actions of p-blockers on blood pressure are complex. After acute administration, blood pressure is only slightly altered. This is because of the compensatory reflex increase in peripheral vascular resistance that results from a (3-blocker-induced decrease in cardiac output. Vasoconstriction is mediated by a-receptors, and a-receptors are not antagonized by (3-receptor blocking agents. Chronic administration of (3-blockers, however, results in a reduction of blood pressure, and this is the reason for their use in primary hypertension (see Chapter 20). The mechanism of this effect is not well understood, but it may include such actions as a reduction in renin release, antagonism of (3-receptors in the central nervous system, or antagonism of presynaptic facilita-tory (3-receptors on sympathetic nerves. 

The exact mechanism of this peripheral adrenergic neuron blocking agent is not well defined. Reserpine administration results in depleted stores of norepinephrine, dopamine, and serotonin in multiple organs. The decreased peripheral resistance and cardiac output that results is manifested as a decrease in blood pressure. A central nervous system (CNS) effect may also play a role in decreasing blood... 

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