Renal Pelvic Afferent Nerves Are Responsible for Greater Resting and Evoked Vasoconstrictor Tone in Individual Rats

Abstract

Greater acute pressor responsiveness to behavioral stress has been observed in those patients susceptible to the development of essential hypertension. Likewise, differences in resting sympathetic tone have been observed with greater tone reflected in higher systemic vascular resistance in many hypertensive patients or those prone to develop hypertension. Since renal denervation (RDN) has been reported to reduce arterial pressure in some patients with resistant hypertension, we sought to define the role of the renal nerves in determining resting and evoked vasoconstrictor tone. We hypothesized that RDN or selective renal pelvic deafferentation (RPDA) would prevent differences in resting vasoconstrictor tone, presumably sympathetic, and prevent greater vasoconstrictor responsiveness to startle in those rats that are hyperreactors to stress. Outbred male Sprague‐Dawley rats were instrumented for arterial pressure, heart rate and cardiac output determination. After recovery, rats were tested for their cardiovascular responsiveness to air jet (20 psi, 1–2 sec) and to cold water stress (1 cm deep for 1 min). Rats were separated into those with larger pressor responsiveness (LP) to startle with air jet or cold water and compared to those with smaller pressor responses (SP). Sympathetic tone was estimated by responses to administration of hexamethonium (20 mg/kg) and by pentolinium (10 mg/kg). LP had greater reductions in arterial pressure after ganglionic blockade due to greater falls in calculated systemic vascular resistance. Subsequently, rats underwent either RDN with extracorporeal radiofrequency ablation of the renal artery (100 KHz, <1 mW, 20 sec duration, 4–6 times/artery) or RPDA with capsaicin infusion in the renal pelvis. One week later, rats were retested for stress responsiveness and sympathetic tone. Either RDN or RPDA prevented the differences observed in pressor responsiveness to startle such that there was no difference between SP and LP. In addition, there were no longer differences between SP and LP in resting vasoconstrictor tone determined with ganglionic blockade. These data suggest that renal pelvic afferent nerves are responsible for greater stress‐induced vasoconstrictor responses and higher vasoconstrictor tone in a subset of rats (LP). We propose that RDN acts selectively in hyperreactors to acute stress (LP) and lowers their overall resting and evoked vasoconstrictor tone to reduce arterial pressure in hypertension due to pelvic afferents. These data suggest that RDN or selective RPDA may be more efficacious in treating this cohort of the population with essential hypertension.Support or Funding InformationSupported by St. Louis University