Vascular Reactivity to Various Vasoconstrictor Agents and Endothelium-Dependent Relaxations of Rat Thoracic Aorta in the Long-Term Period of Pinealectomy

Abstract

Abstract. In this study, the effects of reduced melatonin concentrations in the long-term period of pinealectomy on mean arterial blood pressure (BP) and vascular responses in isolated rat thoracic aorta were investigated. Rats were pinealectomized (Px) two months before the beginning of the studies. Rings of endothelium-intact and -denuded rat arteries were mounted in isolated tissue baths for the measurements of isometric contractile force. No significant difference was determined between the arterial BP of Px (88.1 ± 1.9 mmHg) and control (83.8 ± 1.2 mmHg) rats. All arteries isolated from control and Px rats showed essentially identical contractions in response to phenylephrine, serotonin, calcium, clonidine, vasopressin, and angiotensin-II. Only endothelin-1 (ET-1)-induced contractions in the endothelium-denuded vessels isolated from Px rats were found to be increased to some extent. Pinealectomy did not affect acetylcholine or sodium nitroprusside-induced relaxation in the rat aorta either. These data suggest that reduced melatonin levels two months after pinealectomy did not modify either the vascular reactivity to various vasoconstrictor agents except the partially increased contractile responses to ET-1 in the endothelium-denuded thoracic aortas of Px rats or the endotheliumdependent and -independent relaxations in rat thoracic aorta. Restoration of the increased vascular responses to some vasoconstrictor agents, which were reported previously, may be the reason of why the hypertension is temporary following pinealectomy.

Melatonin and Health: Insights of Melatonin Action, Biological Functions, and Associated Disorders

“…In accord, the elimination of the pineal gland decreased levels of melatonin in circulation and in obese rats elevated body weight as compared to healthy rats after 3 weeks (Prunet-Marcassus et al 2003 ). In normal rats when postoperative duration was increased to 2 months, they gained weight in both the body and the heart (Kurcer et al 2006 ). Melatonin (30 mg/kg/day, i.p.…”

Endothelial dysfunction and melatonin

“…There is also a reduction in the synthesis of endothelium-derived contractile factor (EDCF) with an increase in diameter of isolated arteries. On the contrary, pinealectomized animals show a significantly higher level of endothelin-1 in the thoracic aorta [48,55,56].…”

“…When taken in dosages of 5 or 10 mg/kg it also demonstrates moderate antihypertensive action, which was obvious from the systemic arterial blood pressure registered in healthy animals. Contrary to that, surgical removal of their pineal gland was followed, for some time, with disposition to hypotension [46,48,61].…”

Experimental models of melatonin-deficient hypertension

“…The fact that pinealectomy induces only transitory hypertension is determined by temporary alterations in vascular reactivity. Although vascular responses to norepinephrine, serotonin and angiotensin II were greater than that of control rats one week after pinealectomy but the long-term (two months after pinealectomy) endothelium-intact and -denudated arteries showed almost identical contractions in response to phenylephrine, serotonin, angiotensin II, vasopressin and calcium (42), whereas only endothelin-induced contractions in the endothelium-denudated vessels isolated from the pinealectomized rats were increased (43). This modification in vascular reactivity may be partly induced by metabolic and biochemical changes seen in the pinealectomized animals.…”