The important participation of sympathetic nervous system in various forms of experimental hypertension is well known. This is also true for salt hypertension elicited by excess salt intake in Dahl salt-sensitive rats (for review see Zicha et al. 2012). Two recent studies in Dahl rats (Zicha et al. 2019, Puleo et al. 2020) evaluated the hypothesis on the role of β-adrenergic WNK4-NCC pathway in salt-sensitive hypertension which has been proposed by Mu et al. (2011). Although these studies differed in many experimental details, both of them demonstrated a major importance of α1- rather than β adrenergic mechanisms for the development of salt hypertension in this rat strain.
Zicha et al. (2019) demonstrated that chronic β adrenergic blockade by propranolol did not lower blood pressure (BP) in Dahl salt-sensitive rats developing salt hypertension. It also did not modify their sympathetic component or natriuretic response to acute hydrochlorothiazide administration which inhibited the activity of sodium-chloride cotransporter (NCC). Puleo et al. (2020) reported that chronic β-adrenergic blockade failed to affect salt hypertension development or to reduce renal WNK4-NCC pathway. On the other hand, their study demonstrated the important influence of α1 adrenergic pathway on the activity, expression and phosphorylation of NCC. Chronic α1-adrenergic antagonism by terazosin treatment in Dahl salt-sensitive rats, which started before the onset of high salt intake, considerably attenuated the development of salt hypertension. This treatment diminished BP difference between the salt-loaded Dahl salt-sensitive rats and their control groups by 70-75 %. However, terazosin-treated Dahl salt-sensitive animals fed a high-salt diet had not only suppressed renal NCC activity but they also did not respond to acute phenylephrine administration. This suggests that chronic α1-adrenergic blockade affected both renal sodium retention mechanisms and α1-adrenergic vasoconstriction (Puleo et al. 2020).
It remains to determine how these two mechanisms contribute to salt hypertension in Dahl rats. We found that the acute ganglionic blockade lowered substantially BP of salt hypertensive Dahl rats, abolishing 45-55 % of the BP difference between salt-loaded Dahl salt-sensitive rats and their control groups (Zicha et al. 2019). If we consider the results of both above studies, it seems that the renal contribution might be responsible for about 25 % of BP elevation seen in Dahl salt-sensitive rats developing salt hypertension, whereas α1-adrenergic vasoconstriction contributes to this BP change by about 50 %.
Of course, this consideration is highly speculative. Nevertheless, it might stimulate further effort to distinguish the role of kidney and brain in the pathogenesis of salt hypertension. Perhaps even more promising could be the estimation of renal and extrarenal effects of central sympathoexcitation in Dahl rats (Mark 1991, Gabor and Leenen 2012, Fujita et al. 2009) which is related to central α2-adrenergic mechanisms (Wainford et al. 2015). As far as the role of kidney in the pathogenesis of salt hypertension is concerned (Frame et al. 2019), some attention should also be paid to participation of renal vascular and tubular effects of increased sympathetic tone in these salt hypertensive animals.
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