Role of renal sympathetic nerves in mediating hypoperfusion of renal cortical microcirculation in experimental congestive heart failure and acute extracellular fluid volume depletion.

Abstract

To evaluate the pathophysiologic importance of renal nerves in regulating the renal vasomotor tone, we measured several parameters of renal cortical microcirculation before and after acute renal denervation (DNx) in the following three groups of anesthetized Munich-Wistar rats: (group 1) congestive heart failure after surgically induced myocardial infarction (n = 10), (group 2) acute extracellular fluid volume depletion after deprivation of drinking water for 48 h (n = 8), and (group 3) sham or nontreated controls (n = 6). In the myocardial-infarcted rats, DNx led to a uniform increase in glomerular plasma flow rate of, on average, 36%. Single nephron glomerular filtration rate of myocardialinfarcted rats also increased despite a reduction in glomerular capillary hydraulic pressure. These changes were associated with a fall in arteriolar resistances, particularly in the efferent arteriole. The glomerular capillary ultrafiltration coefficient rose in all but one myocardial-infarcted animal. A similar hemodynamic pattern was seen after DNx in water-deprived animals. In every water-deprived animal, glomerular plasma flow rate and single nephron GFR increased on average by 28 and 14%, respectively. Again, afferent and efferent arteriolar resistances decreased significantly. Furthermore, the ultrafiltration coefficient increased uniformly and substantially with DNx.To ascertain the potential importance of the interaction between the renal nerves and angiotensin II in these circumstances, we compared the renal cortical hemodynamics in additional groups of water-deprived rats (group 4) after DNx (n = 15), (group 5) during inhibition of angiotensin II with saralasin (n = 15), and (group 6) during treatment with both saralasin and DNx (n = 15). No appreciable difference was detected between group 4 vs. 6. In contrast, substantial differences were noted between group 5 vs. 6: on average, the glomerular plasma flow rate was 26% higher and the afferent and efferent arteriolar resistances 25% and 27% lower, respectively, in group 6.Portions of these studies were presented at the annual meeting of the American Society of Nephrology, Washington, DC, 1984, and at the Annual Meeting of the Federations of American Societies for Experimental Biology, Washington, DC, 1985, and were published in abstract form (1984. Am. Soc. Nephrol. 17:134; and 1985. Clin. Res. 33:489A).Address correspondence to Dr. Kon, Laboratory of Renal Physiology.Receivedfor publication 8 January 1985 and in revisedform 12 July 1985.These observations provide direct evidence to indicate pathophysiologic importance of renal nerves in the profound intrarenal circulatory adjustments in prerenal circulatory impairment. The vasoconstrictive effects of renal nerves appear to be mediated in part by their stimulatory influence on angiotensin II release and their direct constrictor actions on pre-and postglomerular vessels as well.

Renal neurohormonal regulation in heart failure decompensation

“…Decreased arterial pressure reduces carotid baroreflex signaling leading to increased sympathetic signaling to the kidney (32). Failure to match cardiac output to increased preload leads to high renal sympathetic nerve activity (RSNA) and its modulation in response to altered circulating blood volume is blunted or abolished (52).…”

Decreased cardiac output, venous congestion and the association with renal impairment in patients with cardiac dysfunction

“…Increased SNS activity will influence GFR by changing the filtrationcoefficient [20,21]. Furthermore, increased SNS activity triggers angiotensin II release, increasing the effect on GFR [21]. Finally, the effect of ANP on preserving GFR by decreasing sensitivity of the tubuloglomerular feedback mechanism is blunted in CHF, thereby compromising GFR [22].…”

Renal Handling of Sodium in the Nephrotic Syndrome

“…Beside all these factors, the sympathetic nervous system influences renal function to produce sodium retention and water reabsorption throughout the entire nephron [62,63] independent of changes in renal hemodynamics. Moreover, acute unilateral renal denervation in rats with congestive heart failure increased urinary flow rate and sodium excretion as a result of decreased net renal tubular sodium and water reabsorption [64], Observations in experimental animal models and humans [65] suggest that increased efferent renal sympathetic nerve activity in nephrotic syndrome contributes to the renal sodium re tention and edema formation. However, in an isolated perfused PAN kidney preparation, a condition in which extrinsic neural factors are eliminated, the urinary excre tion of sodium remained as compared to that in control kidney [46], suggesting that in nephrotic animals the avid sodium retention cannot be entirely explained by sympa thetic nervous system activation.…”