Key result
eNOS inhibitor L-NNA preserves ~73% of baseline coronary flow in adolescent female rats versus adults.
Absolute Event Rate: 73% vs 53%
p-value: p=<0.01
Estrogen-mediated coronary vascular dilatation in adolescent rats is largely dependent on a non-NO pathway, whereas in adult rats it is largely dependent on an NO pathway.
Hypothesis-generating for age-specific estrogen coronary pathways in female rats; leaves open human translation and clinical relevance.
BACKGROUND: Estrogen is known to dilate the coronary vascular system mainly through nitric oxide (NO) release. However, it has not been determined whether or not this effect occurs equally throughout all stages of the female life cycle. We examined the changes in coronary flow properties in adolescent, adult and ovariectomized (OVX) female rats using the endothelial NO synthetase blocker, L-N (omega) nitroarginine (L-NNA). METHODS AND RESULTS: Female rats were divided into 3 groups: adolescent (13 weeks, n=6), adult (19 weeks, n=8) and OVX (20 weeks, n=7, 12 weeks after oophorectomy). Coronary effluent was measured using the Langendorff non-working heart model before and 15 min after the use of L-NNA. In OVX rats, coronary effluent was significantly decreased in comparison with adolescent and adult rats (adolescent vs OVX: p<0.001; adult vs OVX: p<0.05). After treatment with L-NNA, coronary effluent was significantly higher in the adolescent group compared with the adult and OVX groups (adolescent vs adult: p<0.01; adolescent vs OVX: p<0.0005). CONCLUSIONS: Oophorectomy brought about an increase in coronary vascular resistance. L-NNA exacerbated coronary vascular resistance in relation to maturation. It is suggested that the effect of estrogen on vascular dilatation in adolescents is largely dependent on a non-NO pathway, whereas adults are largely dependent on an NO pathway.
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Fukuhara et al. (2006) studied Coronary vascular resistance (n=21). L-N (omega) nitroarginine (L-NNA) vs. Adult and ovariectomized rats was evaluated on Coronary effluent after L-NNA treatment (percentage of pre-treatment flow) (p=<0.01). Treatment with the eNOS inhibitor L-NNA preserved coronary flow significantly more in adolescent female rats (73% of baseline) compared to adult rats (53% of baseline, p<0.01), suggesting age-dependent mechanisms of vasodilation.
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