Endothelial Modulation of Vasoconstrictor Responses in the Perfused Rabbit Ovarian Vascular Bed

Abstract

The purpose of this study was to investigate the effects of endothelial denudation, inhibitors of nitric oxide (NO) and prostanoid synthesis on vasoconstrictor responses in the perfused rabbit ovarian vascular. The experiments were conducted using an in vitro perfusion system, where the ovarian vascular bed (en bloc) was perfused with Krebs’ solution delivered at a constant flow rate using a peristaltic pump. Changes in perfusion pressure, which reflected peripheral resistance, were measured. Results showed that noradrenaline (NA) (10^–9 to 10^–6 mol) induced reproducible dose-dependent vasoconstrictor responses. Vasoconstrictor effects of low doses of noradrenaline were not affected by perfusion of the vascular bed with CHAPS (4.7 mg/ml for 30 s) to remove the endothelium. The same treatment however, significantly reduced responses induced by the higher doses of noradrenaline, thus depressing the maximum response. KCl-induced vasoconstriction was not affected by CHAPS. L-N^G-nitroarginine (L-NOARG) (10^–5 mol/l) enhanced NA-induced vasoconstriction. D-NOARG, the inactive isomer of L-NOARG and aminoguanidine, an inhibitor of inducible nitric oxide synthase reduced rather than enhanced noradrenaline-induced responses. Methylene blue (3 × 10^–5 mol/l) and LY 83583 (10^–5 mol/l) produced a potentiation of NA-induced vasoconstrictor responses. Indomethacin (3 × 10^–6 mol/l) did not significantly enhance NA-induced vasoconstriction. The nonselective endothelin antagonist, SB 209670 (10^–7 and 10^–6 mol/l) did not inhibit the vasoconstriction to NA. In conclusion, results are interpreted to suggest that NA-induced vasoconstriction in the perfused rabbit ovarian vascular bed is accompanied by a release of NO and possibly endothelium-derived contracting factor. There was no evidence for a modulation of vasoconstrictor responses by products of arachidonic acid metabolism or endothelins released from the endothelium.

Renin Uptake by the Endothelium Mediates Vascular Angiotensin Formation

“…11,23 The disadvantage of CHAPS is its capacity to damage the vascular smooth muscle layer. CHAPS did not decreases the response to norepinephrine, but we cannot exclude the possibility that CHAPS had some effect on vasoconstriction, eg, at higher doses of norepinephrine 24 or after Ang II infusion.…”

Ex vivo Reactivity of the Ovarian Vascular Bed to Noradrenaline and Carbachol during Ovarian Hyperstimulation Syndrome

“…Estrogens have been shown to induce vasodilator effects [5] via the release of endothelial nitric oxide (NO). Recent studies have shown that locally released NO modulated ovarian blood flow around the periovulatory period in rats [6] consistent with modulation of ovarian vascular responses by the endothelium [7]. This finding is supported by the observation that NWnitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of NO [8], inhibits human chorionic gonadotropin (HCG)-induced increase in blood flow [6].…”

“…The endothelium-derived relaxing factor has subsequently been identified as NO [24][25][26]. NO has been shown to modulate vascular responses in the ovarian vascular bed [7]. In addition, locally released NO has been shown to modulate blood flow to the ovary during the process of ovulation [6].…”

“…We previously demonstrated that carbachol-induced vasodilation in the ovarian vascular bed is endotheliumdependent since the vasodilator response was abolished when the vascular endothelium was removed by perfusion with CHAPS [7]. We have also shown that both NO and a hyperpolarizing factor (EDHF), the identity of which is yet unknown, mediated carbachol-induced endothelium-dependent vasodilation in the vascular bed.…”