318 research outputs found
Sex differences in pulmonary vascular control: focus on the nitric oxide pathway
Although the incidence of pulmonary hypertension is higher in females, the severity and prognosis of pulmonary vascular disease in both neonates and adults have been shown to be worse in male subjects. Studies of sex differences in pulmonary hypertension have mainly focused on the role of sex hormones. However, the contribution of sex differences in terms of vascular signaling pathways regulating pulmonary vascular function remains incompletely understood. Consequently, we investigated pulmonary vascular function of male and female swine in vivo, both at rest and during exercise, and in isolated small pulmonary arteries in vitro, with a particular focus on the NO-cGMP-PDE5 pathway. Pulmonary hemodynamics at rest and during exercise were virtually identical in male and female swine. Moreover, NO synthase inhibition resulted in a similar degree of pulmonary vasoconstriction in male and female swine. However, NO synthase inhibition blunted bradykinin-induced vasodilation in pulmonary small arteries to a greater extent in male than in female swine. PDE5 inhibition resulted in a similar degree of vasodilation in male and female swine at rest, while during exercise there was a trend towards a larger effect in male swine. In small pulmonary arteries, PDE5 inhibition failed to augment bradykinin-induced vasodilation in either sex. Finally, in the presence of NO synthase inhibition, the pulmonary vasodilator effect of PDE5 inhibition was significantly larger in female swine both in vivo and in vitro. In conclusion, the present study demonstrated significant sex differences in the regulation of pulmonary vascular tone, which may contribute to understanding sex differences in incidence, treatment response, and prognosis of pulmonary vascular disease
Altered purinergic signaling in uridine adenosine tetraphosphate-induced coronary relaxation in swine with metabolic derangement
We previously demonstrated that uridine adenosine tetraphosphate (Up4A) induces potent and partially endothelium-dependent relaxation in the healthy porcine coronary microvasculature. We subsequently showed that Up4A-induced porcine coronary relaxation was impaired via downregulation of P1 receptors
Changes in the nitric oxide pathway of the pulmonary vasculature after exposure to hypoxia in swine model of neonatal pulmonary vascular disease
Neonatal pulmonary vascular disease (PVD) is increasingly recognized as a disease that complicates the cardiopulmonary adaptations after birth and predisposes to long-term cardiopulmonary disease. There is growing evidence that PVD is associated with disruptions in the nitric oxide (NO)-cGMP-phosphodiesterase 5 (PDE5) pathway. Examination of the functionality of different parts of this pathway is required for better understanding of the pathogenesis of neonatal PVD. For this purpose, the role of the NO-cGMP-PDE5 pathway in regulation of pulmonary vascular function was investigated in vivo, both at rest and during exercise, and in isolated pulmonary small arteries
Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade prevent cardiac remodeling in pigs after myocardial infarction: role of tissue angiotensin II
BACKGROUND: The mechanisms behind the beneficial effects of
renin-angiotensin system blockade after myocardial infarction (MI) are not
fully elucidated but may include interference with tissue angiotensin II
(Ang II). METHODS AND RESULTS: Forty-nine pigs underwent coronary artery
ligation or sham operation and were studied up to 6 weeks. To determine
coronary angiotensin I (Ang I) to Ang II conversion and to distinguish
plasma-derived Ang II from locally synthesized Ang II, (125)I-labeled and
endogenous Ang I and II were measured in plasma and in infarcted and
noninfarcted left ventricle (LV) during (125)I-Ang I infusion. Ang II type
1 (AT(1)) receptor-mediated uptake of circulating (125)I-Ang II was
increased at 1 and 3 weeks in noninfarcted LV, and this uptake was the
main cause of the transient elevation in Ang II levels in the noninfarcted
LV at 1 week. Ang II levels and AT(1) receptor-mediated uptake of
circulating Ang II were reduced in the infarct area at all time points.
Coronary Ang I to Ang II conversion was unaffected by MI. Captopril and
the AT(1) receptor antagonist eprosartan attenuated postinfarct
remodeling, although both drugs increased cardiac Ang II production.
Captopril blocked coronary conversion by >80% and normalized Ang II uptake
in the noninfarcted LV. Eprosartan did not affect coronary conversion and
blocked cardiac Ang II uptake by >90%. CONCLUSIONS: Both circulating and
locally generated Ang II contribute to remodeling after MI. The rise in
tissue Ang II production during angiotensin-converting enzyme inhibition
and AT(1) receptor blockade suggests that the antihypertrophic effects of
these drugs result not only from diminished AT(1) receptor stimulation but
also from increased stimulation of growth-inhibitory Ang II type 2
receptors
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