The effects of chronic alterations in plasma adrenaline levels, on the development of a raised blood pressure in young spontaneously hypertensive (SHR) rats, have been investigated. Bilateral adrenal demedullation (at 4 weeks) significantly reduced plasma adrenaline levels and attenuated the development of hypertension. Pressor responses to phenylephrine (0.3-10 micrograms, i.v.), measured in the pithed animals 11 weeks after demedullation, were unaffected although neurogenic pressor responses were significantly reduced. Subcutaneous implants of procaterol and salbutamol (0.005 and 0.165 mumol/kg, respectively) restored hypertension development in demedullated rats and significantly enhanced neurogenic pressor responses, while responses to i.v. phenylephrine remained unaltered, in the pithed rats. Implants of adrenaline (0.165 and 0.5 mumol/kg, s.c.) also restored hypertension development. However, pressor responses to phenylephrine were reduced and neurogenic responses only slightly enhanced when compared to those obtained in untreated pithed demedullated rats. The pro-hypertensive effect of adrenaline (0.5 mumol/kg, s.c.) was abolished by treatment with the beta 2-adrenoreceptor selective antagonist ICI 118551 (25 mg/kg/day, p.o.). In the subsequently pithed rats, neurogenic pressor responses were slightly reduced when compared to those in animals treated with adrenaline alone. In control demedullated rats, ICI 118551 had no effect on blood pressure nor on the neurogenic and phenylephrine-induced pressor responses. However, in sham-operated animals, ICI 118551 attenuated the development of hypertension and significantly reduced neurogenic pressor responses in the subsequently pithed rats. Responses to phenylephrine remained unaltered. The results support the suggestion that a beta 2-adrenoreceptor-mediated facilitation of sympathetic neurotransmission may be involved in mediating the pro-hypertensive effects of circulating adrenaline in the SHR rat.

This paper describes the development of several important modifications that were incorporated into the ultrasonic, transit-time dimension system in order to obtain multiple simultaneous, instantaneous, and continuous measurements of the external dimensions of the aorta and its major branches in conscious, unrestrained animals. At operation a pair of small piezoelectric crystals was sutured to arterial adventitia, and a miniature pressure gauge was implanted in the vessel at the same cross-sectional plane. After recovery from surgery, wall motion was not altered appreciably and scarring was minimal. This technique allows long-term monitoring of aortic pressure-dimension relations and is applicable for small (fetal and neonatal) as well as large (adult dogs and sheep) animals. When vessel wall thickness is measured, stress-radius analysis can be performed so as to compute vascular elastic stiffness as a function of stress. Moreover, the suitability for radiotelemetry of the pressure and dimension signals measured with this technique enables the study of these parameters in unrestrained animals, e.g., during spontaneous severe exercise.

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 ...

Epinephrine has been implicated in the genesis of some forms of hypertension. We have investigated the effects of epinephrine on vasoconstrictor responses evoked by adrenergic stimuli in the isolated perfused rat kidney. Low concentrations of epinephrine (2.5 - 5 X 10(-9) M) increased the amplitude of vasoconstrictor responses evoked by electrical stimulation of the renal adrenergic nerves. These concentrations of epinephrine had no effect on the basal perfusion pressure of the kidney or on the amplitude of vasoconstrictor responses evoked by exogenous norepinephrine. The potentiating effect of epinephrine persisted after infusion of the amine had ceased. Kidneys that had been perfused with 3H-epinephrine accumulated radioactivity, which could then be released by renal nerve stimulation. Cocaine (3 X 10(-5) M) reduced the renal accumulation of 3H-epinephrine and abolished both the persistent potentiating effect of the amine and the release of radioactivity evoked by subsequent nerve stimulation. The potentiating effect of epinephrine infusion was abolished by the beta 2-selective adrenergic receptor antagonist ICI 118,551 (3 X 10(-8) M), but not by the beta 1-selective adrenergic receptor antagonist atenolol (10(-6) M). These results indicate that concentrations of epinephrine that can be achieved during acute stress can enhance the amplitude of neurogenic vasoconstrictor responses. This effect appears to be mediated via a prejunctional beta 2-adrenergic receptor. The persistent nature of this effect may be due to the neuronal accumulation and subsequent release of epinephrine.

In pithed bilateral adrenal demedullated spontaneously hypertensive rats, slow i.v. infusion of adrenaline (500 ng/min) significantly increased pressor responses to the electrical stimulation of the entire sympathetic outflow, but had little effect on pressor responses induced by bolus injections of noradrenaline. After pretreatment with timolol (1 mg/kg, i.v., 30 min) adrenaline infusion enhanced noradrenaline-induced pressor effects, but not stimulation-induced responses. Salbutamol (50-500 ng/min, i.v.) and procaterol (2.5 ng/min, i.v.) infusions significantly potentiated stimulation-induced pressor effects without affecting noradrenaline-induced responses. Higher rates of salbutamol (5 micrograms/min, i.v.) and procaterol (25 ng/min, i.v.) infusion significantly depressed noradrenaline-induced pressor effects and attenuated those induced by sympathetic nerve stimulation. It is concluded that the potentiation of stimulation-induced pressor responses by adrenaline salbutamol and procaterol, involves a beta-adrenoreceptor mediated facilitation of sympathetic neurotransmission.