BRADYKININ AND PROTEIN-KINASE-C ACTIVATION FAIL TO STIMULATE RENAL SENSORY NEURONS IN HYPERTENSIVE RATS

In normotensive rats, renal sensory receptor activation by increased u reteral pressure results in increased ipsilateral afferent renal nerve activity, decreased contralateral efferent renal nerve activity, and contralateral diuresis and natriuresis, a contralateral inhibitory ren orenal reflex response. In spontaneously hypertensive rats (SHR), incr easing ureteral pressure fails to increase afferent renal nerve activi ty. The nature of the inhibitory renorenal reflexes indicates that an impairment of the renorenal reflexes would contribute to the increased efferent renal nerve activity in SHR. We therefore examined whether t here was a general decrease in the responsiveness of renal sensory rec eptors in SHR by comparing the afferent renal nerve activity responses to bradykinin in SHR and Wistar-Kyoto rats (WKY). In WKY, renal pelvi c perfusion with bradykinin at 4, 19, 95, and 475 mu mol/L increased a fferent renal nerve activity by 1066+/-704, 2127+/-1121, 3517+/-1225, and 4476+/-1631% . second (area under the curve of afferent renal nerv e activity versus time). In SHR, bradykinin at 4 to 95 mu mol/L failed to increase afferent renal nerve activity. Bradykinin at 475 mu mol/L increased afferent renal nerve activity in only 6 of 10 SHR. In WKY, renal pelvic perfusion with the phorbol eater 4 beta-phorbol 12,13-dib utyrate, known to activate protein kinase C, resulted in a peak affere nt renal nerve activity response of 24+/-4%. However, 4 beta-phorbol 1 2,13-dibutyrate failed to increase afferent renal nerve activity in SH R. These findings demonstrate decreased responsiveness of renal pelvic sensory receptors to bradykinin in SHR. The impaired afferent renal n erve activity responses to bradykinin in SHR may be due to a lack of p rotein kinase C activation or a defect in the intracellular signaling mechanisms distal to protein kinase C activation.