Nitric oxide and thyroid gland: modulation of cardiovascular function in autonomic‐blocked anaesthetized rats

Abstract

We have previously reported that acute administration of N(G)-nitro-l-arginine methyl ester (L-NAME) increases the mean arterial pressure (MAP) and heart rate (HR) in autonomic-blocked (CAB) anaesthetized rats. In the present study we examined whether thyroid and adrenal glands are involved in these pressor and chronotropic responses. Sprague-Dawley rats were studied after bilateral vagotomy and ganglionic blockade with hexamethonium (10 mg kg(-1)), and stabilization of MAP with infusion of phenylephrine (PE) (6 microg kg(-1) min(-1)). The rats were divided into groups: L, CAB; PE, CAB + PE bolus (6 microg kg(-1)); L-TX, thyroidectomy + CAB; L-AX, adrenalectomy + CAB; TX, only thyroidectomy; C, CAB. L, L-AX and L-TX groups received a bolus of l-NAME (7.5 mg kg(-1)). Triiodothyronine (T3), thyroxin (T4) and thyrotropin (TSH) levels were measured in L and L-TX rats before and after l-NAME administration. Reduced nicotamide adenine dinucleotide (NADPH) diaphorase activity was determined in heart and aorta of the TX group. The pressor response induced by l-NAME was similar in all groups. l-NAME-induced-tachycardia was associated with this rise in MAP. Adrenalectomy did not modify this chronotropic response, but it was attenuated by thyroidectomy. Thyroidectomy by itself decreased the circulating levels of T3 but it had no effect on the plasma levels of T4 and TSH. L and L-TX groups showed similar levels of circulating T4 and TSH, meanwhile the plasma level of T3 decreased in the L group. Nitric oxide synthase (NOS) activity in atria as well as in aorta was greater in the TX group compared with C. When autonomic influences are removed, the thyroid gland modulates intrinsic heart rate via a mechanism that involves, at least in part, the nitric oxide pathway.

Nitric oxide and cardiac function

“…In fact, it has been observed that in the rat with autonomic-blocked N G -nitro-Larginine methyl-ester (L-NAME) administration induces tachycardia, along with an increase in blood pressure. These effects are partially prevented by thyroidectomy and are not affected by adrenalectomy (Fellet et al, 2003(Fellet et al, , 2004. The tachycardic effects of NO inhibition in this rat model are in contrast to those observed by Ward and Angus (1993) in the rabbit.…”

Autonomic regulation of pacemaker activity: role of heart nitric oxide synthases

“…Although NO was recognized primarily as a mediator of endothelial control of vascular smooth muscle, it is conceived as a paracrine autacoid involved in modulation of cardiac autonomic control and contractility (23). The mechanisms by which NO regulates heart contractility and contraction rate and the relations of the heart cycle to NO diffusion between mitochondria and cytosol are physiological processes that are starting to be understood.We have observed that N G -nitro-L-arginine methyl ester (L-NAME) administration to autonomic-blocked rats induces tachycardia, along with an increase in blood pressure, in a physiological process that is partially prevented by thyroidectomy and is not affected by adrenalectomy (18,19). It is well known that the heart is a target organ for thyroid hormones and that alterations in thyroid status influence cardiac contractile and electrical activities by a direct action of triiodothyronine (T 3 ) in cardiomyocyte receptors (16, 38).…”

“…We have observed that N G -nitro-L-arginine methyl ester (L-NAME) administration to autonomic-blocked rats induces tachycardia, along with an increase in blood pressure, in a physiological process that is partially prevented by thyroidectomy and is not affected by adrenalectomy (18,19). It is well known that the heart is a target organ for thyroid hormones and that alterations in thyroid status influence cardiac contractile and electrical activities by a direct action of triiodothyronine (T 3 ) in cardiomyocyte receptors (16,38).…”

Thyroid disorders and nitric oxide in cardiovascular adaptation to hypovolemia

“…According to our results, NO pathway would be involved in this mechanism. Thyroid hormones modulate NO steady-state level which may act as a messenger to modulate the mitochondrial bioenergetic function, resulting in an NO-mediated regulation of the heart pacemaker activity (Fellet et al 2004. Additionally, we demonstrated that hypothyroidism contributes in a differential way to ageing-induced changes in the myocardium and aorta tissues.…”