Factors Influencing the Concentration of Catecholamines at the Receptors

SUMMARY In stroke-prone spontaneously hypertensive rats (SHRSP) plasma norepinephrine levels and vascular reactivity to norepinephrine are increased and intravascular volume is reduced during the developmental phase of hypertension. Since the accelerated rise in blood pressure following sodium-loading in SHRSP cannot be attributed to the volume-retaining properties of sodium, the effects of an increased dietary intake of sodium on biochemical parameters of sympathetic vascular tone were investigated. The following results were obtained. First, the increased reactivity of vascular smooth muscle was further augmented in sodium-treated SHRSP; the degree of supersensitivity was positively correlated to the plasma sodium concentration. After blockade of the neuronal uptake by 30 fiM cocaine, no difference in vascular reactivity to norepinephrine was detected between SHRSP on a normal and SHRSP on a high-sodium diet. Second, the inactivation of norepinephrine by the neuronal uptake was impaired in rats on a high-sodium diet, the impairment being more pronounced in SHRSP than in Wistar-Kyoto (WKY) rats. This decreased inactivation could be expected to cause higher concentrations of the neurotransmitter at the receptor site if the transmitter release from the nerve ending remains constant. Third, the release of norepinephrine and epinephrine into the plasma was increased in sodium-loaded SHRSP but not in sodium-loaded WKY. Cold exposure exaggerates these differences between normotensive and hypertensive rats. These findings suggest that a high-sodium intake modifies the transmission of sympathetic impulses at the level of the nerve terminal in both WKY and SHRSP. In the normotensive rats, moderate impairment of norepinephrine inactivation, however, was balanced by an appropriate reduction in central sympathetic discharge following sodium-loading. In the hypertensive rats, the peripheral disturbance in norepinephrine inactivation due to sodium-loading was obviously not balanced by an adequate withdrawal of central sympathetic discharge. The resultant hemodynamic change was a further increase in the sympathetically mediated vasoconstriction, which is regarded as at least one of the main mechanisms of the sodium-dependent acceleration of hypertension in SHRSP. (Hypertension 4: 773-781, 1982) KEY WORDS • sodium • stroke-prone spontaneously hypertensive rats sympathetic activity • vascular reactivity • norepinephrine metabolism T HE reciprocal relationship between intravascular volume and the degree of vasoconstriction is mediated by changes in the activity of vasopressor systems in response to changes in volume.' Thus, salt-loading, which is accompanied by fluid volFrom the Department of Cardiology, and the Department of Pharmacology, University of Heidelberg, West Germany.Supported by a grant from the Deutsche Forschungsgemeinschaft, Bonn, within the SFB90, Heidelburg.Address for Wolfgang Rascher and Ursula Ganten: Department of Pharmacology, University of Heidelberg, D6900 Heidelberg, West Germany.Address for reprints:...

show abstract

“…Extraneuronal uptake and metabolism were quantitated from the difference before and after additional blockade with corticosterone. 16 …”

Section: Uptake Of 3h-norepinephrinementioning

confidence: 99%

Contribution of the sympathetic nervous system to the hypertensive effect of a high sodium diet in stroke-prone spontaneously hypertensive rats.

Dietz¹,

Schömig²,

Rascher³

et al. 1982

Hypertension

View full text Add to dashboard Cite

show abstract

“…Bilateral adrenalectomy was performiied under ether anestlhesia 24 Determination of plasnma renin activity Plasmna renin activity was determined by radioimmutnoassay from a modification of the method of Haber et al (18). In this method, duplicate 100 ul samples of plasma anticoagulated with 1 mg/ml EDTA were incubated at 37°C for 2 h and the angiotensin I generated was estimated by radioiimmunoassay.…”

Section: Adrenalectomy and Nephrectomymentioning

confidence: 99%

Interactions between angiotensin peptides and the sympathetic nervous system mediating intestinal sodium and water absorption in the rat.

Levens¹,

Peach²,

Carey³

1981

J. Clin. Invest.

View full text Add to dashboard Cite

“…In vas deferens, several drugs and procedures, as for example denervation, intervene in the stimulus-effect relationship (Ariens, 1964;Kasuya, Goto, Hashimoto, Watanabe, Munakata & Watanabe, 1969;Westfall, 1970;Trendelenburg, 1972;Evans, Iwayama & Burnstock, 1973). It has been suggested that in some instances an alteration in the availability of calcium occurs.…”

Section: Antagonism and Potentiation In Terms Of Receptor Theorymentioning

confidence: 99%

Dual Effect of Α‐adrenoceptor Antagonists in Rat Isolated Vas Deferens

Jurkiewicz

1976

British J Pharmacology

View full text Add to dashboard Cite

I In rat isolated vas deferens, the isotonic contractile responses to low doses of noradrenaline or adrenaline were antagonized, and those to high doses were potentiated, by yohimbine, piperoxan, phentolamine and tolazoline. Effects due to intermediate doses were not affected, or were potentiated within about 30 min, following an initial inhibition. 2 The a-adrenoceptor blockers thus caused a shift to the right and an increase of the maximum height of log dose-response curves of a-adrenoceptor stimulants. For a given dose of antagonist, the onset was slower for the potentiating than for the blocking effect. 3 The shift to the right induced by piperoxan and yohimbine on dose-response curves of noradrenaline and adrenaline was analysed with the Schild plot, and the slopes obtained, around 0.3, were lower than expected from receptor theory. When cocaine was used to block neuronal uptake, the slopes were close to 1.0. 4 The increase in maximum response to noradrenaline and adrenaline induced by a-adrenoceptor blockers was dependent on the time of incubation, on the dose of antagonist, and on the initial height of responses to the agonist. A less pronounced potentiation was also obtained when acetylcholine was used as agonist. 5 The findings are explained in terms of receptor theory as being due to a dual effect of aadrenoceptor antagonists; competitive antagonism proper, which may be disclosed after blockade of neuronal uptake, and an interaction at a different locus, which results in potentiation of the effects of noradrenaline and adrenaline.

show abstract

Factors Influencing the Concentration of Catecholamines at the Receptors

Cited by 45 publications

References 38 publications

Contribution of the sympathetic nervous system to the hypertensive effect of a high sodium diet in stroke-prone spontaneously hypertensive rats.

Contribution of the sympathetic nervous system to the hypertensive effect of a high sodium diet in stroke-prone spontaneously hypertensive rats.

Interactions between angiotensin peptides and the sympathetic nervous system mediating intestinal sodium and water absorption in the rat.

Dual Effect of Α‐adrenoceptor Antagonists in Rat Isolated Vas Deferens

Contact Info

Product

Resources

About