Matthew McIntosh

McGill University Health Centre, Montréal, Quebec, Canada

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Publications (2)7.64 Total impact

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    ABSTRACT: Di-(2-ethylhexyl) phthalate (DEHP) is used industrially to add flexibility to polyvinyl chloride (PVC) polymers and is ubiquitously found in the environment, with evidence of prenatal, perinatal and early infant exposure in humans. In utero exposure to DEHP decreases circulating testosterone levels in the adult rat. In addition, DEHP reduces the expression of the angiotensin II receptors in the adrenal gland, resulting in decreased circulating aldosterone levels. The latter may have important effects on water and electrolyte balance as well as systemic arterial blood pressure. Therefore, we determined the effects of in utero exposure to DEHP on systemic arterial blood pressure in the young (2month-old) and older (6.5month-old) adult rats. Sprague-Dawley pregnant dams were exposed from gestational day 14 until birth to 300mg DEHP/kg/day. Blood pressure, heart rate, and activity data were collected using an intra-aortal transmitter in the male offspring at postnatal day (PND) 60 and PND200. A low (0.01%) and high-salt (8%) diet was used to challenge the animals at PND200. In utero exposure to DEHP resulted in reduced activity at PND60. At PND200, systolic and diastolic systemic arterial pressures as well as activity were reduced in response to DEHP exposure. This is the first evidence showing that in utero exposure to DEHP has cardiovascular and behavioral effects in the adult male offspring.
    Toxicology and Applied Pharmacology 11/2012; · 3.98 Impact Factor
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    ABSTRACT: The effect of prolonged hypoxemia in early life on systemic arterial blood pressure at maturity was assessed in Sprague-Dawley rats. Animals hypoxic in early life (12 males, 10 females) were raised in hypoxia (FiO₂ = 0.12) for the first 10 days of life and subsequently raised in normoxia, along with age-matched controls (11 males, 9 females). At 2 months of age, arterial blood pressure was recorded intravascularly using telemetry in awake and unrestrained animals over two 12-h night-time (active) and daytime (resting) periods. Aortic pulse wave velocity was assessed in six additional hypoxic pretreated and five control anesthetized 2-month-old male rats. Systolic, mean, and pulse pressures were significantly greater in the hypoxic pretreated group compared to the control group during resting and active periods in both sexes (P ≤ 0.05). Diastolic pressure and heart rate did not differ between the two groups. Hypoxic pretreated males displayed significantly increased blood pressure variability during the resting period. Aortic pulse wave velocity was also found to be elevated in the hypoxic pretreated rats. Prolonged hypoxic stress in early life in the rat is associated with increased systolic arterial pressure at maturity very likely due to decreased arterial compliance. These findings suggest that a nutrient-independent, postnatal stress may lead to long-lasting vascular alterations predisposing to increased arterial pressure at maturity. This raises the possibility that adult survivors of congenital cyanotic cardiac disease may be at risk for secondary cardiovascular morbidity unrelated to surgical repair or residual cardiac defects.
    American Journal of Hypertension 11/2010; 23(11):1228-33. · 3.67 Impact Factor