Influence of Pituitary, Thyroid, and Adrenal Hormones on Norepinephrine Turnover and Metabolismin the Rat Heart

1 The influence of hormonal and neuronal factors on adrenoceptors mediating increased cardiac force and rate of contraction were studied in rat isolated atria. The pharmacological properties of these receptors were deduced from the relative potencies of agonists and from the effects of selective aand /-adrenoceptor antagonists. The numbers and affinities of a-and /-adrenoceptors were also determined by radioligand binding to ventricular membrane fragments. 2 Hypophysectomy reduced the inotropic potency of isoprenaline and increased the potency of phenylephrine and methoxamine in left atria. The effect of phenylephrine was inhibited by propranolol less effectively and by phentolamine or phenoxybenzamine more effectively in hypophysectomized than in control rats. The difference in block was smaller at low than at high antagonist concentrations. Similar but smaller changes were observed for chronotropic responses of right atria. 3 The decreased /-and increased a-receptor response after hypophysectomy was similar to that observed earlier in thyroidectomized rats (Kunos, 1977). These changes developed slowly after hypophysectomy (>2 weeks), they were both reversed within 2 days of thyroxine treatment (0.2mg/kg daily), but were not affected by cortisone treatment (50 mg/kg every 12 h for 4 days). 6 These results indicate that thyrotropin or steroids do not contribute to the reciprocal changes in the sensitivity of cardiac xl-and /-adrenoceptors in altered thyroid states. These thyroid hormonedependent changes are probably due to a parallel, reciprocal change in the numbers but not the affinities of al-and /3-adrenoceptors. Reciprocal regulation of cardiac alj-and P-adrenoceptors by thyroid hormones requires intact sympathetic innervation but not the presence of normal stores of the neurotransmitter.

Section: Discussioncontrasting

confidence: 68%

The Influence of Hormonal and Neuronal Factors on Rat Heart Adrenoceptors

Kunos

Mucci

O’Regan

1980

“…Thus the rapid decline in 3H-noradrenaline in adrenalectomized or demedullated rats, at 24 hr after its administration, indicates increased noradrenline turnover and synthesis. These results are consistent with those of Landsberg & Axelrod (1968).…”

Section: Discussionsupporting

confidence: 92%

Role of adrenal hormones in the synthesis of noradrenaline in cardiac sympathetic neurones

Bhagat

1969

. Adrenalectomy or adrenal demedullation affected neither the levels of endogenous catecholamines in the rat heart nor the accumulation of 3H‐noradrenaline 1 hr after its intravenous administration. . Twenty‐four hours after intravenous administration of labelled amine, however, its retention was markedly reduced in the heart of adrenalectomized or demedullated rats. Ganglionic blockade prevented this reduction. . Rate calculations from the decline of catecholamine levels after blockade of synthesis with α‐methyl‐tyrosine showed that cardiac synthesis of noradrenaline increased about four‐fold after demedullation and about three‐fold after adrenalectomy. This increase in synthesis may compensate for the loss of circulating catecholamines. . There was no change in catechol‐o‐methyl‐transferase activity, but monoamine oxidase activity was increased in the homogenates of the heart of adrenalectomized and demedullated rats. The increase in the cardiac monoamine oxidase activity was markedly greater in the adrenalectomized rats than in the demedullated rats. . It is suggested that adrenal cortex insufficiency may modulate the rate of synthesis of noradrenaline and monoamine oxidase activity in cardiac sympathetic neurones.

“…Alternatively, hypothyroidism might be involved as Tahiliani & McNeil (1985) have reported depressed plasma levels of both T3 and T4 in 6-week streptozotocin-diabetic rats and hypothyroidism has been found to increase cardiac sympathetic activity whether measured by [3H]-NA turnover or, as here, by tissue NA decline following AMPT (Landsberg & Axelrod, 1968). Na', K+-ATPase activity has been reported to be depressed by hypothyroidism and increased by T3 administration (Norgaard et al, 1983).…”

Section: Discussionmentioning

confidence: 63%

“…Such a hypothesis does not, however, explain its prevention by MI or Statil unless such treatment prevented the hypothyroidism. The elevation of tissue NA in the absence of AMPT is unlikely to be due to hypothyroidism since Landsberg & Axelrod (1968) found no NA elevation in their hypothyroid rats and Ganguly et al (1987) found no effect of T3 administration on the elevated tissue NA which they observed in diabetic rats. The latter paper reported a decrease in the proportion of [3H]-NA recovered from a cardiac tissue fraction containing the storage vesicles.…”

Section: Discussionmentioning

confidence: 84%

Tissue noradrenaline and the polyol pathway in experimentally diabetic rats

Lucas

Qirbi

1989

1 The effects of a six week period of streptozotocin-induced diabetes on tissue catecholamines and on in vivo noradrenaline turnover were assessed in rats. 2 Noradrenaline concentrations measured in heart ventricle, terminal ileum, vas deferens, spleen and adrenal tissue from the diabetic rats were all found to be elevated compared to those found in control rat tissues. The adrenaline contents of the adrenal glands were also raised in these animals. 3 Noradrenaline turnover in heart ventricle, terminal ileum and vas deferens was estimated from the decline in tissue content of the amine following inhibition of its synthesis with a-methyl-ptyrosine. Turnover was found to be increased in all three tissues. 4 The involvement of the polyol pathway in the above changes was investigated by examining the effects of continuous treatment with an aldose reductase inhibitor, Statil (ICI 128436) or dietary myo-inositol supplementation. Either treatment was found to prevent or reduce the increases in tissue noradrenaline and in its turnover. Myo-inositol treatment also partially prevented the rise in adrenal adrenaline. 5 It is concluded that the elevation of tissue catecholamines and of noradrenaline turnover by diabetes was related to myo-inositol depletion secondary to excessive sorbitol synthesis. Possible mechanisms for the observed increase in noradrenaline turnover could involve Na', K+-ATPase depression.