The effect of bilateral adrenal demedullation on vascular reactivity and blood pressure in spontaneously hypertensive rats

Abstract

1Bilateral adrenal demedullation of juvenile spontaneously hypertensive rats attenuated, but did not prevent, the development of hypertension. Neither did it affect the subsequent vascular reactivity to phenylephrine though it significantly reduced the vascular effects of sympathetic nerve stimulation. an effect which is inhibited by the P-adrenoceptor antagonist propranolol (Stjarne & Brundin, 1975).More recently, Majewski, Tung & Rand (1981) have shown that rats, implanted with a slow release depot preparation of adrenaline, develop an elevated blood pressure which can be prevented by the concomitant administration of metoprolol, suggesting a possible role for circulating adrenaline in the development of hypertension. Such an involvement might explain the prevention of development of a raised blood pressure in spontaneously hypertensive (SHR) rats by chronic treatment with propranolol, as observed by Kubo, Esumi & Ennyu (1977).The removal of circulating adrenaline by adrenal demedullation might prevent the development of genetic hypertension or lower the blood pressure in hypertensive animals and the experiments described here were performed to test these hypotheses. AnimalsMale spontaneously hypertensive (SHR) rats, originating as a hypertensive mutant of the WistarKyoto Japanese strain (Okamoto & Aoki, 1963), were obtained just after weaning (i.e. 3 weeks old). Some animals were operated on one week later (body weight 50-60 g) while others were used when adult (body weight 250-325 g).Bloodpressure measurement (a) Indirect To assess the development of hypertension in young rats, systolic blood pressures (SBP) were monitored twice weekly using a non-invasive tail-cuff method in animals anaesthetized with ether.Pressures were recorded at room temperature (-20°C) without preheating the rats. The tail cuff was inflated and deflated using a manual sphygmomanometer and the tail arterial pulse, detected using a photoelectric pulse sensor (Medical Physics Lab., Leicester Royal Infirmary) placed distal to the cuff, was displayed on an oscilloscope (Tektronix 5 103N). The end points used to determine SBP were © The Macmillan Press Ltd 1983 430 K.R. BORKOWSKI & P. QUINN cessation of blood flow during cuff inflation and its resumption during deflation and the average of the two values was recorded.Initial control SBP's were determined on three separate occasions in the first week after weaning.The juvenile rats were then divided-randomly into two groups and bilateral adrenal demedullation of one group (n = 7) was performed under ether anaesthesia via flank incisions. The adrenal gland was exposed, a small incision made in the cortex and enucleation performed by gentle squeezing with forceps. A second group of animals (n = 6) was shamoperated at the same time. After surgery, SBP's were determined by the above method twice weekly (Tuesday and Friday at 09 h 00 min-h 00 min) over a period of twelve weeks.(b) Direct in conscious rats In a separate series of experiments, adult rats were prepared for direct recording of blood ...

Studies on the adrenomedullary dependence of κ‐opioid agonist‐induced diuresis in conscious rats

“…Thus, the effectiveness of adrenal demedullation was assessed by measuring plasma adrenaline and adrenal gland catecholamine content. In agreement with previous studies (Borkowski & Quinn, 1983;Blackburn et al, 1986), surgical enucleation significantly reduced plasma adrenaline and adrenal gland catecholamine levels, indicating effective removal of the adrenal medulla. Whilst not measured in the present study, plasma corticosterone is unaffected by demedullation (Borkowski & Quinn, 1983;Blackburn et al, 1986) indicating that the adrenal cortex remains functional and appears not to be involved in the diuretic response to c-opioid agonists.…”

“…Under Saffan (alphaxolone/alphadolone; 12mg kg-, i.v.) anaesthesia, bilateral adrenal demedullation was performed by methods described previously (Borkowski & Quinn, 1983). Seven days later, a carotid artery and a jugular vein were catheterized, under Saffan anaesthesia, to facilitate arterial blood sampling and intravenous drug administration respectively.…”

Comparison of Ca2+ Currents of Chromaffin Cells from Normotensive Wistar Kyoto and Spontaneously Hypertensive Rats

“…The adrenal medulla's role in the origin and maintenance of hypertension in SHR is unclear: bilateral adrenalectomy of pre-hypertensive and adult SHR produced normotensive animals, even though some BP reduction was also observed in WKY rats (Aoki et al 1973). Bilateral removal of the adrenal medulla (demedullation) in pre-hypertensive juvenile SHR attenuated the hypertension developed in the adult (Borkowski and Quinn 1983), whereas demedullation in hypertensive adult SHR either had no effect Quinn 1983, Aoki et al 1973) or lowered BP (Sakaguchi et al 1983). When sympathectomized SHR are demedullated, BP returned to normotensive levels (Lee et al 1991).…”

α2-Adrenoceptor-Mediated Inhibition of Catecholamine Release from the Adrenal Medulla of Spontaneously Hypertensive Rats is Preserved in the Early Stages of Hypertension

“…Hypertension and left ventricular hypertrophy were absent only in sympathectomized SHR that were subjected to adrenal demedullation [15,16]. Studies have also shown that the development of hypertension is attenuated in young SHR subjected to adrenal demedullation [17,18] and that the development of hypertension is restored by chronic adrenaline supplementation [19]. However, we have previously shown that in SHR before (6 weeks of age) and during the development of high blood pressure (12 and 22 weeks of age) not only are adrenal catecholamine content and synthesis reduced but also that adrenaline plasma levels are similar compared with those found in the normotensive control Wistar Kyoto (WKY) rats [20].…”