Renal sympathetic nerve activity and cardiovascular responses to classical conditioning and high dietary sodium intake in rats

Evidence from electrical stimulation and denervation studies suggests that the renal nerves contribute greatly to hypertension in many experimental models of this disease and appear to play a role in human hypertension as well. However, the interaction between renal sympathetic nerve activity (RSNA) and cardiovascular function during behavioral stress and the effect of high salt diet on these measures has been poorly documented. Two experiments were conducted to investigate differences in RSNA, mean arterial pressure (MAP) and heart rate (HR) responses to classical conditioning in rats differing in genetic predisposition to hypertension and in rats subjected to high dietary salt intake.

A total of 48 animals, 12 spontaneously hypertensive rats (SHR), 12 normotensive Wistar-Kyoto (WKY) rats and 24 borderline hypertensive rats (BHR) at 12-14 weeks of age, were studied in the conscious state during discriminative conditioning. One half (N=12) of the BHR were subjected to8% high salt diet for 8 weeks prior to measurement. Animals were given 5 days of habituation and conditioning with 5 trials of pulsed tone (eventually to become the positive conditioning stimulus, or the CS+) that was associated with tail-shock and 5 trials of an otherwise identical, but continuously-sounded tone (eventually to become the negative conditioning stimulus, or CS-) that was never associated with tail-shock, both 15 sec in duration. After a 48 hour recovery period from the catheterization and renal nerve electrode implantation, RSNA, MAP and HR were measured continuously for ten conditioning trials (5 CS+ and 5 CS- trials, each 30 sec in length). Cardiovascular and renal measurements for each trial included a 9 sec baseline, a 15 sec tone presentation period, and a 6 sec period following the termination of the tone.

A similar pattern of responses in RSNA, HR and MAP was observed in all group of animals during each trial type, but the magnitude of the responses differed depending on group and trial type. Overall, tone onset caused an abrupt sudden burst of RSNA which was followed by an increase in HR and MAP within 5 sec. This was followed by a quiet neural traffic period and a bradycardic/depressor response. This pattern suggests an increase in parasympathetic and a decrease in sympathetic activity through a baroreflex control mechanism. A sustained pressor/bradycardic response consistent with higher sympathetic and parasympathetic activity were also observed in all animals in the remaining seconds of the tone period.

With regard to the influences of genetic predisposition, it was concluded that (1) genetic predisposition determines baseline MAP, but not HR or RSNA levels; (2) genetic predisposition determines reactivity of RSNA, HR and MAP to stress; (3) the RSNA, MAP and HR responses to the two trial types (CS+ and CS-) can be effectively discriminated and animals can establish behavioral responses to stress through a learning process; (4) SHR may have a higher receptor sensitivity to norepinephrine and epinephrine, and/or a vascular defect when compared to WKY and BHR; (5) though SHR, BHR and WKY have comparable total baroreflex gain in MAP in response to conditioned and unconditioned stimuli, the set point is shifted differently, depending on their genetic predisposition, to a higher level during continued conditioning stimulation; and (6) sympathetic activity is dominant over parasympathetic activity in blood pressure regulation during continued conditioning stimulation.

The effect of high dietary sodium (8% NaCl) intake was tested only in the BHR strain. From these results, it was concluded that (1) high salt diet increases baseline MAP, but not HR or RSNA; (2) high salt diet does not change the general pattern of responses in RSNA, HR, and MAP to classical conditioning; (3) high salt diet enhances the learned responses in RSNA to behavioral stress during sudden burst and tone period; (4) high salt diet enhances the conditioned response in MAP; however, the enhanced pressor response appears to be diminished by the baroreflex during the tone period; (5) the unconditioned responses and startle responses in MAP and HR are not affected differentially by dietary sodium intake; and (6) it seems that high salt diet does not change the tonic level or reactivity of heart rate in BHR.