Neural control of renal function in health and disease

The renal sympathetic innervation of the kidney exerts significant effects on multiple aspects of renal function, including renal haemodynamics, tubular sodium and water reabsorption and renin secretion. These effects constitute an important control system which is important in the physiological regulation of arterial pressure and total body fluid and sodium homeostasis. Abnormalities in this regulatory mechanism have pathophysiological consequences and are manifest in clinically relevant human disease states. Decreased renal sympathetic nerve activity results in impaired renin secretion, the inability to conserve sodium normally and an attenuated ability to dispose of both acute and chronic sodium loads. Increased renal sympathetic nerve activity contributes significantly to the excess renal sodium retention and related renal abnormalities observed in both hypertension and oedema forming conditions, such as cardiac failure, cirrhosis and nephrotic syndrome.This paper is based on a lecture given by Dr G. F. DiBona to the Clinical Autonomic Research Society in November 1993     

ALTERATIONS IN CEREBROSPINAL FLUID SODIUM AND OSMOLALITY IN RATS DURING ONE-KIDNEY, ONE-WRAP RENAL HYPERTENSION

Measurements of plasma and cerebrospinal fluid (CSF) sodium and osmolality were made throughout the course of one-kidney, one-wrap Grollman renal hypertension. Although the plasma sodium and osmolality did not rise after 28 days, CSF sodium and osmolality was increased significantly at 3 days postwrap. As a result, the CSF to plasma ratio for both sodium and osmolality was significantly elevated during the initial postwrap period. These observations suggest that an increase in CSF sodium may provide an initiating stimulus for an elevated arterial pressure in one-kidney, one-wrap renal hypertension.     

Energetics of sodium transport in toad urinary bladder.

The ratio of the rate of transepithelial sodium transport, JNa, across the isolated toad urinary bladder to the simultaneously measured rate of transport-dependent metabolism, JsbCO2, has been measured as a function of the transepithelial electrical voltage, deltapsi. The ratio remains constant with a mean value of 18 to 20 over the range of imposed voltages of 0 to +70 mV. With increasing hyperpolarization of the bladder, JNa decreases and the calculated electromotive force or apparent "ENa" of the sodium pump increases. From thermodynamic and kinetic arguments it is shown that the apparent "ENa" approaches the maximal electrochemical potential gradient, ENa, against which sodium can be transported by this tissue only when JNa approximately 0. At this unique condition F ENa (in which F is the Faraday constant) is the maximal free energy of the chemical reaction driving sodium transport and thus equal to the maximal extramitochondrial phosphorylation potential and the maximal free energy of the mitochondrial respiratory chain within the transporting cells.     

Effect of arterial baroreceptor denervation on sodium balance

During chronic increased dietary sodium intake, arterial baroreceptors buffer against sustained increases in arterial pressure, and renal sympathoinhibition contributes importantly to the maintenance of sodium balance by decreasing renal tubular sodium reabsorption and increasing urinary sodium excretion. The present study examined the effect of arterial baroreceptor denervation on sodium balance in conscious rats during low, normal, and high dietary sodium intake. Compared with measurements made before arterial baroreceptor denervation, arterial baroreceptor-denervated rats had similar sodium balance during normal dietary sodium intake but significantly more negative sodium balance during low dietary sodium intake and significantly more positive sodium balance during high dietary sodium intake. At the end of the high dietary sodium intake period, arterial pressure (under anesthesia) was 159+/-5 mm Hg after arterial baroreceptor denervation and 115+/-1 mm Hg before arterial baroreceptor denervation. Sham arterial baroreceptor denervation in time control rats had no effect on sodium balance or arterial pressure during the different dietary sodium intakes. These studies indicate that (1) arterial baroreceptor denervation impairs the ability to establish sodium balance during both low and high dietary sodium intake, and (2) arterial baroreceptor denervation leads to the development of increased arterial pressure during high dietary sodium intake in association with increased renal sodium retention.     

Role of neuropeptide Y in renal sympathetic vasoconstriction: studies in normal and congestive heart failure rats

Sympathetic nerve activity, including that in the kidney, is increased in heart failure with increased plasma concentrations of norepinephrine and the vasoconstrictor cotransmitter neuropeptide Y (NPY). We examined the contribution of NPY to sympathetically mediated alterations in kidney function in normal and heart failure rats. Heart failure rats were created by left coronary ligation and myocardial infarction. In anesthetized normal rats, the NPY Y(1) receptor antagonist, H 409/22, at two doses, had no effect on heart rate, arterial pressure, or renal hemodynamic and excretory function. In conscious severe heart failure rats, high-dose H 409/22 decreased mean arterial pressure by 8 +/- 2 mm Hg but had no effect in normal and mild heart failure rats. During graded frequency renal sympathetic nerve stimulation (0 to 10 Hz), high-dose H 409/22 attenuated the decreases in renal blood flow only at 10 Hz (-36% +/- 5%, P <.05) in normal rats but did so at both 4 (-29% +/- 4%, P <.05) and 10 Hz (-33% +/- 5%, P <.05) in heart failure rats. The glomerular filtration rate, urinary flow rate, and sodium excretion responses to renal sympathetic nerve stimulation were not affected by high-dose H 409/22 in either normal or heart failure rats. NPY does not participate in the regulation of kidney function and arterial pressure in normal conscious or anesthetized rats. When sympathetic nervous system activity is increased, as in heart failure and intense renal sympathetic nerve stimulation, respectively, a small contribution of NPY to maintenance of arterial pressure and to sympathetic renal vasoconstrictor responses may be identified.     

Micropuncture studies of the recovery phase of myohemoglobinuric acute renal failure in the rat

Micropuncture studies of the recovery phase of glycerol-induced myohemoglobinuric acute renal failure were performed in rats whose blood urea nitrogen (BUN) had fallen at least 20% below its peak value. The glomerular filtration rate (GFR) of individual nephrons in a single kidney in the recovery period generally either was in the normal range or minimal. Each animal's BUN concentration at the time of the study was inversely related to the proportion of functioning surface nephrons, but did not correlate with individual nephron GFR values. Proximal tubule fractional water absorption was significantly depressed as manifested by both depressed inulin (TF/P) values and supernormal volumes of collections, a finding which, in the absence of a urea-induced osmotic diuresis, suggests impaired sodium transport by the damaged nephron. The mean proximal tubule hydrostatic pressure in recovery was normal and there was little variation in pressure among functioning nephrons. It is concluded that recovery from this model of acute renal failure reflects the progressive recruitment of increasing numbers of functioning nephrons. The recovery of individual nephron glomerular filtration, once begun, was rapid and complete. No evidence could be adduced that the gradual return of renal function towards normal reflects a slow release of tubular obstruction or repair of disrupted tubular epithelium. Rather, recovery appeared to be directly attributable to the return of an adequate effective glomerular filtration pressure. Significant limitation in proximal tubule water absorption persisted after individual nephron GFR had returned to normal or supernormal values in this model of experimental acute renal failure in the rat, a finding which readily accounts for the diuresis associated with the recovery phase of this syndrome.