Recent insights into the interactions between the baroreflex and the kidneys in hypertension

Abstract

Recent findings in chronically instrumented animals challenge the classic concept that baroreflexes do not play a role in the chronic regulation of arterial pressure. As alterations in renal excretory function are of paramount importance in the chronic regulation of arterial pressure, several of these recent studies have focused on the long-term interactions between the baroreflex and the kidneys during chronic perturbations in arterial pressure and body fluid volumes. An emerging body of evidence indicates that the baroreflex is chronically activated in several experimental models of hypertension, but in most cases, the duration of these studies has not exceeded 2 wk. Although these studies suggest that the baroreflex may play a compensatory role in attenuating the severity of the hypertension, possibly even in primary hypertension with uncertain causes of sympathetic activation, there has been only limited assessment of the quantitative importance of this interaction in the regulation of arterial pressure. In experimental models of secondary hypertension, baroreflex suppression of renal sympathetic nerve activity is sustained and chronically promotes sodium excretion. This raises the possibility that the renal nerves may be the critical efferent link for baroreceptor-induced suppression of central sympathetic output through which long-term compensatory reductions in arterial pressure are produced. This contention is supported by strong theoretical evidence but must be corroborated by experimental studies. Finally, although it is now clear that pressure-induced increases in baroreflex activity persist for longer periods of time than previously suggested, studies using new tools and novel approaches and extending beyond 2 wk of hypertension are needed to elucidate the true role of the baroreflex in the pathogenesis of clinical hypertension.

Renal Denervation Does Not Abolish Sustained Baroreflex-Mediated Reductions in Arterial Pressure

“…However, according to the concept of the renal body-fluid mechanism for long-term control of arterial pressure, these autonomic responses, even if sustained chronically, would not be expected to produce a persistent fall in arterial pressure unless they were associated with a simultaneous effect to enhance the pressure natriuresis mechanism, because otherwise the kidneys would retain fluid until arterial pressure returned to control levels. 8,11 Strong experimental support for this notion comes from a study in dogs in which the renal perfusion pressure to 1 kidney was servocontrolled at a reduction in pressure comparable to that achieved in the present study. 18 Throughout the duration of this study (12 days), there was a sustained reduction in sodium excretion in the kidney with the reduced renal perfusion pressure and an increase in sodium excretion in the high-pressure contralateral kidney.…”

“…8,11 According to this concept, if sodium intake is constant, long-term changes in arterial pressure are not possible unless there is a shift in the pressure natriuresis mechanism. The current study tested the hypothesis that inhibition of renal sympathetic nerve activity is the critical signal emanating from the central nervous system that increases pressure natriuresis and leads to a sustained fall in arterial pressure during prolonged baroreflex activation.…”

“…1,8,[21][22][23] Reduced renal excretory function in denervated kidneys may result from the diminished actions of several natriuretic agents, including NO and endothelin. 24,25 Another possibility is that this relative impairment in sodium excretion in denervated kidneys may reflect renal denervation supersensitivity, which may have diminished functional significance during prolonged activation of the baroreflex.…”

“…[1][2][3][4][5][6][7][8][9][10] These studies, conducted over several weeks, indicate that baroreflex resetting is incomplete in experimental models of hypertension. They also indicate that during chronic increases in arterial pressure, there is sustained baroreflex-mediated suppression of renal sympathetic nerve activity and attendant increments in renal excretory function, responses expected to attenuate the severity of hypertension.…”

“…8,11 Thus, the primary goal of this study was to test the hypothesis that long-term reductions in MAP during prolonged baroreflex activation are critically dependent on intact renal innervation. To this end, the carotid baroreflex was electrically activated in the same dogs both before and after bilateral renal denervation.…”