Sympathetic modulation of renal blood flow by rilmenidine and captopril: central vs. peripheral effects

Abstract

Renal blood flow (RBF) is modulated by renal sympathetic nerve activity (RSNA). However, agents that are supposed to reduce sympathetic tone, such as rilmenidine and captopril, influence RBF also by direct arteriolar effects. The present study was designed to test to what extent the renal nerves contribute to the renal hemodynamic response to rilmenidine and captopril. We used a technique that allows simultaneous recording of RBF and RSNA to the same kidney in conscious rabbits. We compared the dose-dependent effects of rilmenidine (0.01-1 mg/kg) and captopril (0.03-3 mg/kg) on RBF and RSNA in intact and renal denervated (RNX) rabbits. Because rilmenidine and captopril lower blood pressure, studies were also performed in sinoaortically denervated (SAD) rabbits to determine the role of the baroreflex in the renal hemodynamic response. Rilmenidine reduced arterial pressure, RBF, and RSNA dose dependently. In intact rabbits (n = 10), renal conductance (RC) remained unaltered (3 +/- 5%), even after the 1-mg/kg dose, which completely abolished RSNA. In RNX rabbits (n = 6), RC fell by 18 +/- 5%, whereas in SAD rabbits (n = 7) RC increased by 30 +/- 20% after rilmenidine. In intact rabbits, captopril increased RSNA maximally by 64 +/- 8%. RSNA did not rise in SAD rabbits. Despite the differential response or absence of RSNA, captopril increased RC to a comparable degree (maximally 40-50%) in all three groups. Using spectral analysis techniques, we found that in all groups, independently of ongoing RSNA, captopril, but not rilmenidine, attenuated both myogenic (0.07-0.25 Hz) and tubuloglomerular feedback (0.01-0.07 Hz) related fluctuations in RC. We conclude that, in conscious rabbits, the renal vasodilator effect of rilmenidine depends on the level of ongoing RSNA. Its sympatholytic effect is, however, blunted by a direct arteriolar vasoconstrictor effect. In contrast, the renal vasodilator effect of captopril is not modulated by ongoing RSNA and is associated with impairment of autoregulation of RBF.

Renal nerves dynamically regulate renal blood flow in conscious, healthy rabbits

“…But, beyond the lack of a statistical basis to make any strong conclusions on this matter, TGF is also notoriously difficult to assess by dynamic autoregulation (16).While further studies using proximal tubular perfusion to assess TGF in INV and DDNx animals would be interesting, it is also very possible that the classic autoregulatory mechanisms become more active but not stronger to maintain steady-state RBF after renal denervation. In addition, renin-angiotensin system blockade by angiotensin-converting enzyme inhibition increases admittance gain in the TGF band in both anesthetized rats (25) and conscious rabbits (28), and the removal of sympathetically mediated renin release is a possible explanation for this similar trend in our study.…”

“…One study used hexamethonium in dogs (32) while the other used rilmenidine in rabbits (28). Neither study found a significant change in the AP-RBF transfer function after systemic sympatholysis, but this finding is confounded by the fact that both drugs eliminate not only renal sympathetic vasomotion but also sympathetic LF AP oscillations.…”

“…Based on previously published studies of RBFV and dynamic autoregulation in rabbits (28,39), TGF operates between 0.02 and 0.08 Hz, MR operates between 0.08 and 0.20 Hz, the low-frequency (LF) band where sympathetic vasomotion gives rise to the so-called Mayer waves ranges from 0.20 to 0.46 Hz, and the high-frequency (HF) band encompassing the respiratory frequency ranges from 0.76 to 1.5 Hz. Normalized spectra were obtained by expressing power as a percentage of the total power.…”

Effects of Brimonidine Ingestion on Cardiovascular Responses and Renal Function in Conscious Dogs

“…While Stranhoy (1985) showed that RVR increased in response to either α 1 -or α 2 -adrenergic agonists, renal sympathetic nerves might not be stimulated in our study due to the central sympathoinhibitory effect of this drug. A study using an α 2 -adrenoceptor agonist, rilmenidine, demonstrated that the renal nerve was attenuated after drug administration (Janssen et al, 2001). The absence of sympathetic outflow results in limited response of renal arterioles for BP reduction.…”

AGE formation blockade with aminoguanidine does not ameliorate chronic allograft nephropathy

“…After midline incision renal blood flow (RBF) was measured using the Transonic system placed at the left renal artery as previously described (Janssen, et al 2002).…”