The central nervous system (CNS) consists of the brain and spinal cord. The peripheral nervous system (PNS) is the miles of nerves that connect the central nervous system (CNS) to the sensory organs (such as the eye and ear), other organs of the body, muscles, blood vessels and glands. The PNS system is divided into 2 categories, somatic– conscious/voluntary control (control of muscles/joints) and autonomic–subconscious/thoughtless control (control of heart rate/ blood pressure).
The autonomic nervous system is further defined as consisting of three major parts: sympathetic, enteric, and the parasympathetic system. The sympathetic state is the body’s flight or fight response to stress. When triggered by stress the sympathetic symptoms affect different organs of the body and leads to:
- Pupil dilation
- Dry mouth
- Increased heart rate
- Increased blood pressure
- Blood vessel constriction
- Glucose release in liver
- Peristalsis of digestive tract
- Increased kidney secretion of renin and decreased renal blood flow
Conversly in the parasympathetic state, the body is calmer with lower blood pressure and heart rate.
Anatomy of Renal Sympathetic Nervous System
The kidneys are intimately involved in the regulation of the sympathetic nervous system. There are efferent (taking nerve impulses away from the nervous system to muscles and glands) and afferent (taking nerve impulses from sense organs to the nervous system) connections between the kidney and the brain.
The sympathetic outflow or efferent signals originates from multiple central nuclei including paraventricular nucleus of hypothalamus, locus ceruleus, rostral and caudal ventrolateral medulla, pontine and medullary raphe nuclei. The presynaptic sympethatic nerve fibers travel in the spinal cord to the coeliac and superior mesenteric ganglion. A dense network of postganglionic efferent renal nerves course alongside the renal artery and enter the hilum of the kidney. Thereafter, they divide into smaller nerve bundles following the blood vessels and penetrate the cortical and juxtamedullary areas in the kidney. There the nerves innervate efferent and afferent arterioles of Bowman’s capsule, tubular epithelial cells and the juxtaglomerular apparatus (JGA).1
Afferent or sensory nerve fibers from the kidney travel along with the sympathetic nerves at the level of the kidney and then enter the dorsal root ganglia, T6-L4. From here the postsynaptic neuron project at both spinal and supraspinal levels. Most of the brainstem regions involved in cardiovascular control including the hypothalamus receive inputs from the renal afferents.1
Both afferent and efferent nerve fibers are intermixed in the renal nerve plexus embedded in the adventitia and the surface of the renal arteries.
Sympathetic Nervous System and Hypertension
How the Sympathetic Nervous System Effects the Kidney and the Role of Kidneys In Hypertension:
Kidneys play a vital role in the regulation of intravascular volume and blood pressure. Kidneys influence blood pressure control mainly by following 3 pathways, each of which is directly affected by the sympathetic nervous system.
- Pressure natriuresis (auto-regulation of renal arterial flow),
- Renin Angiotensin Aldosterone System (RAAS)
- Sympathetic tone modification
Pressure natriuresis: The auto regulation of the intrinsic renal artery pressure and perfusion influences the natriuresis and thus regulates the sodium excretion (urine volume) intravascular blood volume. Norepinephrine released from the post-synaptic efferent renal sympathetic nerves stimulates alpha 1 adrenergic receptors and leads to vasoconstriction of the afferent arteriole in the Bowman’s capsule, thus reducing renal blood flow and affecting the natriuresis and urine volume. Reduced blood flow stimulates renin secretion.
RAAS: Renin Angiotensin Aldosterone System (RAAS) is nature’s design to respond to the changing hemodynamics in the human body. When renal artery perfusion decreases it activates RAAS and increases renal perfusion by increasing intravascular volume and perfusion pressure (Figure). When stimulated by the norepinephrine released from efferent sympathetic nerves, the B1 receptors on the juxtaglomerular apparatus secrete renin and contribute to hypertension.2
Sympathetic Tone: Reduction in the renal artery perfusion leads to generation of the afferent sympathetic nerve signals, which in turn amplifies central or systemic sympathetic outflow and further affects the blood pressure regulation.2
How the Sympathetic Nervous System Effects the Cardiovascular System:
Increased central sympathetic activity leads to stimulation of alpha and beta receptors in the myocardium. By positive inotropic and chronotropic effect the sympathetic nervous system (SNS) leads to increased contractility of myocardium and increased heart rate, which increases cardiac output and blood pressure. Stimulating alpha 1 receptors in the sympathetic nervous system also leads to systemic vasoconstriction and increased systemic peripheral vascular resistance, thus to increased blood pressure.2
Crosstalk between Renal Nerves and CNS
Chronic Overactivity of the Sympathetic Nervous System in Patients with HTN:
Systemic post-ganglionic sympathetic neural activity can be objectively measured by microneurography or single-unit efferent sympathetic nerve activity/muscle sympathetic nerve activity (s-MSNA). In comparison to normotensive patients, patients with high normal BP, white-coat hypertension, borderline HTN, essential HTN (stage I-3) and essential HTN with LVH were seen to have statistically significant higher s-MSNA (Figure).3
Adapted from: Smith P et al. Am J Hypertens 2004; 17 (3): 217-222.
Increased renal sympathetic activation enhances noradrenaline production and can be measured by norepinephrine spillover. Renal denervation results in reduction of up to 95% of the spillover, demonstrating that the ablation of the renal nerves decrease the crosstalk between the kidney and the brain.4
Effect Of Chronic Systemic and Renal Sympathetic Nervous System Overactivity
Heart: Chronic inotropic and chronotropic stimulation along with systemic hypertension leads to left ventricular hypertrophy > diastolic dysfunction>diastolic heart failure > left atrial enlargement> atrial fibrillation or arrhythmia. Hypertensive heart disease can progress to systolic heart failure and ventricular arrhythmia.
Blood Vessels: Chronic increased tone of the vascular smooth muscle, arterial sclerosis, decreased elasticity or compliance, promotes atherosclerosis.
Kidney: Decreased renal artery perfusion or renal ischemia, decreased renal filtration, increased renin secretion, decreased GFR (glomerular filtration rate), proteinuria, nephrosclerosis, medical renal disease, and chronic renal insufficiency can progress to end stage renal disease (ESRD) (Figure).
Chronic Effect of Increased Sympathetic Nerve Activity
- Esler M. The sympathetic nervous system through the ages from Thomas Willis to resistant hypertension.Exp Physiol. 2011;96:611-622.
- Schlaich MP, et al. Renal denervation as a therapeutic approach for hypertension: novel implications for an old concept. Hypertension. 2009;54:1195-1201
- Bunte M, Oliveira E, Shishehbor M. Endovascular treatment of resistant and uncontrolled hypertension. J Am Coll Cardiol Intv. 2013;6:1-9.
- Smith, P et al. Relationship between central sympathetic activity and stages of human hypertension. Am J Hypertens. 2004;17:217-222.