Guanethidine Induced Sympathectomy in the Adult Rat. II. Functional Effects Following Chronic Administration

Abstract

Guanethidine sulphate in doses of 5 and 40 mg/kg was administered intraperitoneally to adult rats daily for three months followed by discontinuation of administration for one day or three months. Following guanethidine 40 mg/kg a loss of approximately 95 % of the nerve cells of the superior cervical ganglion was observed. No changes were observed after 5 mg/kg. The average mean arterial blood pressure (measured under chloralose‐urethane anaesthesia) was lowered by 33 and 54 mmHg by guanethidine 40 mg/kg for three months followed by discontinuation for one day and three months respectively. The heart rate was unchanged. Guanethidine 5 mg/kg did not change any of these parameters. The increase in blood pressure and heart rate caused by intravenously administered noradrenaline was greatly enhanced following guanethidine 40 mg/kg, whereas only small changes were observed following 5 mg/kg. Following discontinuation for one day of 40 mg/kg for three months the potency ratios for the mean arterial blood pressure and the mean heart rate were 31 and 21 respectively, after discontinuation for three months 44 and 17 respectively. The potency ratios following guanethidine 5 mg/kg were 1.5 to 2.0. No changes were observed in the weight of the suprarenal glands following guanethidine. The present investigation has demonstrated an almost total chemical sympathectomy by guanethidine 40 mg/kg for three months and a persistent hypersensitivity to noradrenaline even after discontinuation of medication for three months.

Somatotopic Organization and Intensity Dependence in Driving Distinct NPY-Expressing Sympathetic Pathways by Electroacupuncture

“…The commonly used reserpine depletes transmitter release from sympathetic neurons via blockage of vesicular monoamine transporters; however, this drug can cross the brain-blood barrier and inhibit the release of dopamine, noradrenaline, serotonin and histamine in the brain (Yaffe et al, 2018). 6-hydroxydopamine and guanethidine more selectively block peripheral sympathetic neurons (Nielsen, 1977;Thoenen and Tranzer, 1973), but are unable to target noradrenergic neuron subtypes. Nor do they have major impact on adrenal sympathetic chromaffin cells (Johnson and O'Brien, 1976;Kolibal-Pegher et al, 1994).…”

The Influence of an Adrenergic Antagonist Guanethidine on the Distribution Pattern and Chemical Coding of Caudal Mesenteric Ganglion Perikarya and Their Axons Supplying the Porcine Bladder

“…Several studies have demonstrated that chronic treatment of either newborn or adult rats by high doses of GUA, causes destruction of peripheral sympathetic neurons (i.e., a kind of pharmacological sympathectomy) [ 68 , 69 , 70 ]. For example, it has been shown that GUA produced a marked depletion of sympathetic neurons in the celiac/mesenteric and superior cervical ganglia [ 71 ].…”

Control of blood pressure in the absence of sympathetic nerves: Is it all about increased variability?

“…A fascinating outcome not explored fully by the authors was the lack of change in baseline BP in the sympathectomy only control group 5 . Mean BP responses in otherwise normal sympathectomized animals have been reported as unaltered 12,16 or showing quite varied levels of reduced BP 13,14 . Recording techniques will account for much of this variability and the long‐term recording telemetry results presented by Augustyniak et al.…”

“…Remodelling of the vascular wall has been shown to occur after sympathectomy, with a decrease in the contractile mass of resistance arteries, 1 and regional haemodynamic changes have been described 12 . Furthermore, in the absence of sympathetic nerves fibres, not only does a supersensitivity of the vasculature to circulating adrenaline develop, 13,14 but the efferent contribution of sensory fibres to the control of BP is enhanced, with increased sensory neuropeptide expression allowing them a greater vasodepressor role 15 . These established structural and functional changes must be considered when interpreting the changes in BP seen in sympathectomized animals after renal injury, with the subsequent responses therefore not wholly attributable to a lack of sympathetic innervation.…”

“…5 Mean BP responses in otherwise normal sympathectomized animals have been reported as unaltered 12,16 or showing quite varied levels of reduced BP. 13,14 Recording techniques will account for much of this variability and the long-term recording telemetry results presented by Augustyniak et al 5 are likely highly reliable. What, then, controls baseline mean arterial pressure in the absence of a functional sympathetic vascular innervation?…”