Role of Renal Nerves in Afferent Arteriolar Reactivity in Angiotensin-Induced Hypertension

Abstract

The objective of this study was to determine the contrlbutlon of renal nerves to the enhanced afferent arterlolar reactivity observed m anglotensm II (Ang II)-induced hypertension Unmephrectomlzed Sprague-Dawley rat3 were divided mto four groups sham rats, renal-denervated rats, Ang II-Infused (at 40 nglmm for 13 days) rats, and Ang II-mfused+renal-denervated rats With the use of an Implanted arterial catheter, mean arterial pressure (MAP) was momtored m conscious rats Ang II Infusion resulted m a progressive increase In MAP from 982 I (day 0) to 16627 mm Hg (day 13) This Increase In MAP was attenuated tn denervated rats and averaged 136?3 mm Hg on day 13 Kidneys were harvested on day 13 for mlcloclrculatory expenments or measurement of mtrarenal Ang II levels Basal afferent arterlolar diameter was similar in all groups, and group averages ranged from 19 6 to 20 7 pm Chrome Ang II Infusion increased mtrarenal Ang II levels Renal denervatlon did not alter this effect Increasing perfusion pressure from 100 to 160 mm Hg reduced afferent artermlar diameter slgnlficantly by I I 250 6% m the sham group and by a similar degree m the remaining three groups Superfusion with Ang II (10 nmol/L) reduced afferent arterlolar diameter by 34 3+2 0% m the sham group This response was enhanced m Ang II-Infused (62 353 4%) but not in renal-denervated or Ang II-mfused+renal-denervated rats Addmonally, the enhanced afferent arteriolar reactivity to Ang II wa$ not Influenced by adrenerglc receptor blockade The afferent artenolar response to noreplnephrme wa? enhanced m renal-denervated, Ang II-infused, and Ang II-mtused+renal-denervated rats compared with sham controls Admmlstratlon of the calcium lonophore A23187 decreased afferent arterlolal diameter slmllarly m all four groups These results indicate that renal nerves contribute to the development of hypertension and to the enhanced afferent artellolar responsiveness to Ang II ehclted by chronic Ang II mfu\lon (Hypertenwn. 1997;29[part 2]:442-449.)

Selective Increase in Renal Arcuate Innervation Density and Neurogenic Constriction in Chronic Angiotensin II-Infused Rats

“…This confirms previous observations in which the slow pressor response to Ang II was reduced after denervation of the kidney. 10,11 Although the greater number of non-contacting sympathetic nerve varicosities found in the electron microscopy studies is the most economical explanation for the increase in the nerve-evoked constrictions, the present study cannot exclude the possibility that a reduction in re-uptake of released norepinephrine by varicosities contributes to the enhanced responses.…”

“…8,9 There is increasing evidence that Ang II may cause changes in the structure of renal blood vessels and in their innervation. 10,11 We found that 6 weeks of inhibition of Ang II production using enalapril in rabbits led to a marked increase in the density of innervation, as well as phenotypic transformation of smooth muscle cells in the wall of 20-to 35-m diameter afferent arterioles into renin-containing secretory cells. 12 Casellas et al 13 subsequently found that infusion of doses of Ang II that have immediate pressor effects reduced the density of the plexus innervating renal vessels in rats across a wider range of vessel diameters (30 to 300 m).…”

Renal Renin-Angiotensin System

“…Both endogenous and exogenous NOs counteract afferent and efferent arteriolar constrictor responses to Ang II [48]. Although afferent arteriolar responses to Ang II were enhanced in Ang II-induced hypertension [50], the buffering effects of endogenous NO on the Ang II-induced vasoconstriction was greater in afferent arterioles than in efferent arterioles [48] and thus contributes to maintaining the renal circulation under conditions of elevated systemic Ang II levels [51].…”

“…These results indicate that increases in the post-glomerular interstitial Ang II concentration can enhance proximal tubular reabsorption and increase preglomerular resistance. Studies using the juxtamedullary nephron preparation demonstrated that in Ang II-infused hypertension, afferent arteriolar responsiveness to Ang II administered from the interstitial side is significantly enhanced [50]. In addition, RIF Ang II levels may play an important role in the pathogenesis of tubulointerstitial changes when levels are inappropriately elevated [64].…”

Mechanical stretch potentiates angiotensin II-induced proliferation in spontaneously hypertensive rat vascular smooth muscle cells

“…3,4 The AngII-augmented vascular response is not specific to SHR, in either the prehypertensive or the established hypertensive phases, and it has been demonstrated in other models of hypertension, including stroke-prone SHR, renal hypertensive rats, deoxycorticosterone acetate/salt-hypertensive rats and AngII-infused hypertensive rats. [5][6][7][8] These findings suggest that the vascular response to AngII is activated in a hypertensive state.…”