Augmented sympathetic nerve activity and pressor responsiveness in DOCA hypertensive rats.

Abstract

SUMMARY Spike potentials in abdominal sympatheticDenes were recorded together with aortic blood pressure before and during electrical stimulation of the posterior hypothalamus in urethane-anesthetized rats. Both the initial rate of sympathetic nerve firing and the subsequent acceleration produced by hypothalamic stimulation were higher in deoxycorticosterone acetate (DOCA) hypertensive than in normotensive rats. Pressor responsiveness was generally augmented, but responses to hypothalamic stimulation were increased far more than those to injected noreplnephrine. Vasodepression produced by blocking autonomlc ganglia pharmacologically with pentolinium was also more pronounced in DOCA hypertensive rats than in normotensive controls. These results support the conclusion that a centrally induced sympathetic hyperactivity is important for maintaining the blood pressure elevation in rats with established DOCA hypertension. conflicting but almost equally popular views now exist on whether sympathetic hyperactivity participates in causing deoxycorticosterone acetate (DOCA) hypertension. Supporting the belief that sympathetic hyperactivity is essential, the hypotension induced by combining adrenalectomy with chemical sympathectomy has been shown to result in identical blood pressure levels in adult normotensive and DOCA hypertensive rats. 1 Also, to restore blood pressure levels following splanchnicotomy during pentobarbital anesthesia, the splanchnic nerves had to be stimulated at much higher frequencies in DOCA hypertensive than in other rats. s Furthermore, destruction of central catecholaminergic neurons through intracerebroventricular injection of 6-hydroxydopamine prevents not only the elevation in tail-cuff systolic pressure 3 but also the attendant increase in plasma norepinephrine* in unanesthetized DOCA hypertensive rats. On the contrary, however, others have found DOCA hypertension either unaffected in adult rats Received January 22,1979; revision accepted September 17,1979. worse in neonates 79 after chemical sympathectomy. Observations that seem contradictory have also been made in our laboratory: DOCA hypertensive rats have an enhanced pressor responsiveness to hypothalamic stimulation, 10 yet their pressures fell only to the same levels as those of normotensive rats when the hypothalamus was destroyed. 11 In an attempt to find a logical explanation for this, we recorded sympathetic nerve activity directly before and during hypothalamic stimulation. To determine if the sympathetic overactivity thereby revealed would account for the elevation in blood pressure, we also measured vasodepression occurring after pentoliniuminduced ganglion blockade. MethodsFemale Sprague-Dawley rats, 3 weeks old, were purchased from Charles River Breeding Laboratories (Wilmington, MA). Soon after arrival, all were anesthetized with sodium amobarbital (8 mg/100 g i.p.) and their left kidneys removed. Silicon rubber molds containing DOCA (200 mg/kg) were implanted subcutaneously in eight rats, according to the method of Ormsbee ...

Role of γ-Aminobutyric Acid (GABA)Aand GABABReceptors in Paraventricular Nucleus in Control of Sympathetic Vasomotor Tone in Hypertension

“…In this regard, sympathetic nerve activity is elevated in animal models of hypertension including spontaneously hypertensive rats (SHRs), renin transgenic rats, Dahl salt-sensitive rats, and deoxycorticosterone acetate-salt rats as well as in hypertensive patients (Judy et al, 1976;Takeda and Bunag, 1980;Greenwood et al, 1999;Mancia et al, 1999;Cabassi et al, 2002). However, the mechanisms underlying heightened sympathetic outflow in hypertension remain poorly understood.…”

Chronic Low-Dose Angiotensin II Infusion Increases Venomotor Tone by Neurogenic Mechanisms

“…[7][8][9][10] Angiotensin II (Ang II) has been identified as a humoral factor implicated in activating the sympathetic nervous system in human hypertension 11,12 ; and the pressor response to infusion of chronic low-dose Ang II in animals has been shown, at least in part, to be sympathetically driven. [13][14][15] Advances have been made in the elucidation of the central pathways involved in mediating this sympathoexcitatory effect, suggesting that systemically delivered Ang II likely activates critical circumventricular organs 16 -19 with efferent projections to brain centers known to influence sympathetic nervous system activity.…”

Abnormal pressure natriuresis. A cause or a consequence of hypertension?

“…However, because mineralocorticoids and Ang II almost invariably raise total peripheral vascular resistance, the high blood pressure has also been postulated to be caused by direct or indirect effects of these agents to constrict the peripheral vasculature. 27 - 30 For example, mineralocorticoids have been postulated to activate the sympathetic nervous system or to stimulate the release of a ouabain-like circulating inhibitor of sodium-potassium adenosine triphosphatase secondary to volume expansion, 31 ' 32 changes that are believed to cause peripheral vasoconstriction and hypertension. The escape from sodium retention has also been postulated to be independent of increased arterial pressure and to be mediated by increased formation of various natriuretic factors, such as a ouabain-like natriuretic hormone, ANF, kinins, prostaglandins, or reduced renal sympathetic nerve activity.…”