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Neural Regulation of the Kidney
The renorenal reflexes have an inhibitory action on excitatory reflexes. Renal mech-
anosensory nerves lower efferent renal sympathetic nerve activity (ERSNA) and
increase urinary sodium excretion, an inhibitory renorenal reflex. There is an inter-
action between efferent and afferent renal nerves, whereby increases in ERSNA
increase afferent renal nerve activity (ARNA), leading to decreases in ERSNA by
activation of the renorenal reflexes to maintain low ERSNA to minimize sodium
retention [ 23 ].
Sympathetic neural regulation of renin release and fluid reabsorption may influ-
ence fluid balance and, in the longer term, the level at which blood pressure is set.
The imbalance in the sympathetic neural innervation of these mechanisms is
involved in resistance to antihypertensive medication [ 24 ].
Therapeutic correlation Recently, bilateral selective renal sympathetic denervation
has been performed for patients with resistant hypertension, yielding several bene-
fits in decrease of renal norepinephrine spillover and renin activity, with increase in
renal plasma flow and overall prolonged reduction of blood pressure. The procedure
consists in ablation through radio frequency of the afferent and efferent innervation
of the kidney, with consequent isolation of renal parenchymal and juxtaglomerular
structures from abnormal stimulation of the efferent adrenergic system, thus sever-
ing the link between the over-activated efferent adrenergic system and the renal
structures involved in regulation of blood pressure [ 25 , 26 ].
The kidney is also involved in the development of salt-sensitive hypertension,
common in the elderly, diabetics, African-Americans, and obese patients, which
increases the risk for glomerulosclerosis and renal failure, as a result of augmented
glomerular capillary pressures. An important component of the fine autoregulation
mechanism of renal blood flow, the myogenic response, consists of the constriction
of the afferent arteriole triggered by increases in perfusion pressure, which, due to
its very short activation delay, can be used in the isolation of glomerular capillaries
from the variations in renal perfusion pressure. The myogenic response is mediated
by the action of extracellular ATP on P2X receptors, their activation being mediated
by 20-hydroxyeicosatetraenoic acid (20-HETE) [ 27 ]. There are several researches
that investigate the involvement of 20-HETE in the control of arterial pressure, reg-
ulation of vascular tone and of renal function, as well as protection of glomerular
permeability barrier [ 28 ]. The impaired ability of the kidney to synthesize 20-HETE
leads to an increased Na+ transport in the proximal tubule and thick ascending loop
of Henle, which consequently generates sodium retention, generating salt-sensitive
forms of hypertension.
Therapeutic correlation Given the significant evidence that substantiates the role
of 20-HETE in hypertension, new therapies have been established based on antihy-
pertensive agents that function as inhibitors of synthesis of 20-HETE and 20-HETE
agonists and antagonists (such as 20-hydroxyeicosa-5(Z),14(Z)-dienoic acid (5-,14-
,20-HEDE), N-[20-hydroxyeicosa-5(Z),14(Z)-dienoyl]glycine (5-,14-,20-HEDGE)
A. Burlacu and A. Covic