Hypothalamic pressor responses and salt-induced hypertension in Dahl rats.

Abstract

Interactions between abnormal salt intake and central sympathetic function were studied by recording pressor and sympathetic effects of hypothalamic stimulation in Dahl salt-resistant (DR) and salt-sensitive (DS) rats. All DS rats, including those fed a low-salt diet since weaning, became hypertensive by 11 weeks of age. Increased salt intake aggravated hypertension in DS rats without affecting blood pressure in DR rats. Basal sympathetic tone determined during urethane anesthesia, from the frequency of splanchnic nerve potentials as well as the magnitude of hypotension induced by a-adrenergic blockade with phentolamine, was consistently lower in low-salt DR rats than in any others. Pressor responses to electrical stimulation of the ventromedial hypothala-mus, whether expressed as absolute or percent increases in mean pressure, were invariably enhanced in DS rats. On the other hand, attendant increases in sympathetic nerve firing were significantly higher in DS rats, but only when expressed as absolute changes and not when expressed as percent changes. Consequently, pressor and sympathetic responses became dissociated in magnitude such that low-salt DR rats which had the weakest pressor responses also had the highest percent increases in sympathetic nerve firing. Peripheral increases in cardiovascular reactivity were considered unlikely because pressor responses to drugs like norepinephrine, tyramine, and vasopressin, were unaltered. Although 5-week-old DS rats that had not been exposed to high-salt intake remained normotensive, basal sympathetic activity and pressor responsiveness to hypothalamic stimulation were already enhanced. Since sympathetic and hypothalamic enhancement occurred before any other changes could be detected it was considered possible that sympathetic hyperactivity of hypothalamic origin may be involved in initiating genetic hypertension. These results also suggest that induction of hypertension in DS rats might depend on genetic transmission of hypersensitivity not only to salt but also to stressful stimuli. (Hypertension 5: 460-467, 1983) KEY WORDS • blood pressure • heart rate • high-salt diet • genetic hypertension • salt-sensitive Dahl rats • sympathetic hyperactivity • ventromedial hypothalamus A FTER Dahl and his associates succeeded in breeding two rat strains with opposite genetic predispositions to salt-induced hyperten-sion, they used parabiotic rats to show that the hyper-tension was due to a renal pressor substance. 1 2 Other mechanisms were not ruled out, however, and it remains possible that sympathetic dysfunction may also be involved. In Dahl salt-sensitive (DS) rats maintained on high-salt intake, vasoconstrictor responsiveness to sympathetic nerve stimulation becomes selectively enhanced as does the fall in vascular resistance resulting after sympathetic denervation. 3 Moreover, peripheral sympathectomy induced by either 6-hy-droxydopamine 4 or guanethidine 5 prevents subsequent elevation of blood pressure and vascular resistance. Concomitant elevation in DS rats of renal ...

Failure of salt loading to inhibit tissue norepinephrine turnover in prehypertensive Dahl salt-sensitive rats.

“…38 Taken together, these observations are consistent with the hypothesis that protection against the development of hypertension in DR fed high NaCl is related to inhibition of sympathetic nervous system activity. VOL 12, No 6, DECEMBER 1988 In contrast, in the DS dietary NaCl loading has been reported to potentiate the increment of vascular resistance in response to sympathetic nerve stimulation 39 and electrical stimulation of the ventromedial hypothalamus, 40 to increase the rate of basal neural firing of the splanchic nerve, 40 and to exacerbate impairment of baroreceptor reflex control of heart rate. 4142 Augmentation of cardiac norepinephrine turnover rate by NaCl loading, after the onset of hypertension, has also been reported in other models of salt-dependent hypertension.…”

Sympathetic neural contribution to salt-induced hypertension in Dahl rats.

“…29 Further intracerebral ventricular injection of hypertonic NaCl solution or angiotensin II produces greater pressor responses in DS than DR rats even before the development of hypertension. 30 Koepke et al 31 have identified an important interaction between environmental factors (such as stress and dietary salt) and genetic factors in the central nervous system control of renal function in DS rats.…”

Chronic central versus peripheral ouabain, blood pressure, and sympathetic activity in rats.

“…2 - 4 Brain OLA content is higher in spontaneously hypertensive rats (SHR) than Wistar-Kyoto (WKY) rats, and high sodium intake further increases brain OLA in SHR. 4 Augmented sympathetic activity has been documented in several forms of sodiumdependent hypertension, including Dahl salt-sensitive (DS) rats 5 and SHR. 6 Brain OLA may play a primary role in mediating the sympathoexcitatory and hypertensive effects of high sodium intake in SHR 7 and DS rats.…”