Impaired reflex response to volume expansion in NaCl-sensitive spontaneously hypertensive rats.

Abstract

Abnormal baroreceptor reflex function that antedates or is a consequence of NaCl loading could contribute to the NaCI-induced exacerbation of hypertension in NaCI-sensitive spontaneously hypertensive rats (SHR-S). The current study tested the hypothesis that an impairment in cardiopulmonary baroreceptor reflex function exists in SHR-S before NaCl loading. The reflex response to volume expansion was compared in SHR-S, NaCI-resistant SHR (SHR-R), and normotensive Wistar-Kyoto (WKY) and Sprague-Dawley rats maintained on a normal NaCl diet. Conscious, free-moving SHR-S, SHR-R, WKY, and Sprague-Dawley rats were volume expanded with whole blood to 15% of blood volume within 6 minutes, and mean arterial pressure, heart rate, and lumbar sympathetic nerve activity were recorded. Heart rate and lumbar sympathetic nerve activity decreased significantly in SHR-R, WKY, and SpragueDawley rats after volume expansion. In contrast, in SHR-S neither heart rate after volume expansion nor lumbar sympathetic nerve activity was significantly different from levels before volume expansion. The blunted reflex response of heart rate and lumbar sympathetic nerve activity to volume expansion suggests impaired cardiopulmonary volume receptor function in SHR-S. This likely contributes to NaCI-induced hypertension in SHR-S on a high NaCl diet. {Hypertension 1989;14:518-523) T he severity of hypertension increases in NaCIsensitive spontaneously hypertensive rats (SHR-S) fed a high NaCl diet. 12 These animals have elevated plasma norepinephrine levels and exaggerated depressor responses to ganglionic blockade compared with SHR-S on a "normal" NaCl diet, suggesting that the NaCI-induced exacerbation of hypertension is related to increased peripheral sympathetic nervous system activity. In contrast, blood pressure is not altered by a high NaCl diet in NaCI-resistant SHR (SHR-R).3 It appears that the NaCI-induced increase in blood pressure in SHR-S is, at least in part, related to reductions in noradrenergic input and norepinephrine turnover in the anterior hypothalamic area.2 '

Atrial natriuretic peptide regulation of noradrenaline release in the anterior hypothalamic area of spontaneously hypertensive rats.

“…Noradrenaline release from nerve terminals in other brain regions is not altered in the SHR consuming a high NaCl diet, and AHA noradrenaline release is not altered in response to dietary NaCl supplementation in NaCl-resistant rodent strains, e.g., Wistar Kyoto rats (WKY). Since SHR have a severely blunted cardiopulmonary baroreflex response (14) and the baroreflex activates noradrenergic neurons in the brainstem (15,16), we initially speculated that the reduction in noradrenaline release in the AHA of SHR fed a high NaCl diet resulted from blunted baroreflex activation of noradrenergic neurons in the brainstem that projected to the AHA. However, the vast majority of noradrenergic neurons that send axons to the AHA also project to other surrounding nuclei (i.e., the lateral and posterior hypothalamic areas) that do not display a decrease in extracellular noradrenaline in high NaCl fed SHR (unpublished data from our group).…”

“…A second experiment tested more directly the role of endogenous ANP in this model by infusing into the AHA c-ANP, (ANP [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] ), a peptide fragment of ANP that binds to the ANP clearance receptor (ANP-C) and thereby decreases the ability of the ANP-C receptor to bind to and take up endogenously released ANP. This results in an elevation of extracellular ANP in the AHA.…”

Excitatory sympathetic reflex in NaCl-sensitive spontaneously hypertensive rats.

“…We hypothesized that one such influence may be persistent blunting of the cardiopulmonary reflex, which has previously been shown by our laboratory to be impaired in SHR-S before high NaCl exposure. 13 If the cardiopulmonary reflex remained blunted in the SHR-S during dietary NaCl supplementation, it would facilitate the NaClinduced increase in MAP. The following protocol was designed to test this hypothesis.…”

Sympathetic Activity in Dahl Salt-Sensitive Hypertension - Why is a Nitric Oxide-Induced Inhibitory System Up-Regulated in the Sympathetic Center?

“…Enhanced Na + accumulation leads to a negative spiral in which sympathetic nerve activity is increased and in turn promotes further Na + reabsorption [18]. Because a high-salt diet inhibits the volume receptor reflex in the cardiopulmonary region [25,26], Na + ion excretion is further inhibited by this response. However, surprisingly, Na + ions do not accumulate in the body of salt-sensitive hypertensive Dahl rats once they become hypertensive [27].…”