This study investigated the effects of selective estrogen receptor (ER) agonists on constrictor prostanoid (CP) function and on the development of mean arterial pressure (MAP) in aortic coarctation-induced hypertension (ACIH). Female Sprague-Dawley rats were divided randomly into four groups: intact (INT), ovariectomized (OVX), OVX + ERα selective agonist (4, 4’, 4”-(4-Propyl-[1H]-pyrazole-1, 3, 5-triyl)trisphenol; OVX+PPT), or OVX + ERβ selective agonist (2,3-bis(4-Hydroxyphenyl)-propionitrile; OVX+DPN). Rats were then subjected to abdominal aortic coarctation (hypertensive, HT) or sham surgery (normotensive, NT). PPT, DPN or vehicle treatments were given daily as a subcutaneous injection. MAP was measured every other day at 2-14 days after coarctation. Mesenteric arterioles were harvested 12-14 days after coarctation for isometric tension studies to examine concentration-responses to VP. Basal and VP-stimulated prostanoid release and mRNA and protein levels of ERα and ERβ (using real time RT-PCR and immunoblotting) were measured in separate groups of arterioles. MAP was higher in INT-HT, OVX+PPT-HT and OVX+DPN-HT than in OVX-HT after 12 days. Vascular reactivity to VP was greater in OVX+PPT-NT rats than in other groups. There were no significant differences in vascular reactivity to VP in HT groups. Blockade of thromboxane receptor (TP) with SQ 29,548 (TP receptor antagonist) did not have a significant effect in any groups. Inhibition of intracellular calcium release with simvastatin (blocker of IP3 mediated calcium release) was greater in NT than in HT groups, and greater in OVX- and DPN-treated groups than in INT and PPT-treated groups. VP-stimulated release of thromboxane (TXA2) and prostacyclin (PGI2) were highest in INT-HT and OVX+PPT-HT rats. Neither mRNA nor protein expression of ERs changed significantly in response to selective ER agonist treatment or during hypertension. Selective ERα stimulation with PPT during development of ACIH resulted in similar effects to those seen in INT rats for CP release, VP reactivity of mesenteric arterioles and MAP, while selective stimulation of ERβ only increased MAP. While ERα is capable of modulating most of the effects of estrogen on the vasculature, ERβ has stimulatory effects on MAP during the development of ACIH that merit further investigation. Further studies of the vascular actions of ERα and ERβ may lead to better hormonal therapies that successfully prevent and/or treat cardiovascular disease in post-menopausal women.

Consumption of pulse crops has been linked to improvements in blood vessel function, but which pulse variety/type is better and how they work remains unknown. Two distinct studies were conducted to address these questions. In study 1, spontaneously hypertensive rats (SHR) were fed control diet, or diets containing 30% (w/w) beans, peas, lentils, chickpeas, or mixed pulses. Normotensive Wistar-Kyoto (WKY) rats were fed the control diet. The lentil–containing diet significantly attenuated the rise in BP (+8 and +31 mmHg, vs. control) and reduced large artery remodeling compared to control. In study 2, SHR were fed control, mixed lentil, green lentil, or red lentil diets for 8 weeks. WKY were fed control or mixed lentil diets. Green lentils decreased arterial remodeling and improved arterial compliance in the SHR. A diet high in green lentils could be a valuable adjunct to allopathic medicine to mitigate effects of hypertension on the vasculature. / October 2013

published_or_final_version / Physiology / Master / Master of Philosophy

No description available.

No description available.

This study aimed to determine whether a functionally appropriate cell type, renal proximal tubule (PT) cells, displayed Na⁺/Li⁺ countertransport activity, and if so, to characterise the exchange mechanism further and delineate any relationship with the NHE. Both freshly isolated rat PT cells and primary cultures of rabbit PT cells demonstrated SLC activity. Since Li⁺ can take the place of Na⁺ in various different exchange mechanisms, the contribution of the Na⁺/K⁺ ATPase and NHE to the measured SLC activity was shown to be minimal with the use of specific inhibitors for these transporters. Kinetic parameters could not be determined in these experiments, however, as Li⁺ efflux from cells was shown to be extremely rapid and initial rates of efflux could not be accurately determined. To further investigate the possibility of SLC and NHE being associated transporters, we wished to measure protein expression of NHE1 and NHE3 in rabbit PT cells and correlate this with erythrocyte and PT cell SLC activity. Failure to detect either NHE isoform in the rabbit PT cells, however, prevented completion of these experiments. Evidence to suggest a possible link between SLC and NHE activity arose through investigation into signalling mechanisms affecting SLC activity. Similar to previous published data on the inhibitory effect of cAMP upon NHE activity, human erythrocyte SLC K_m and V_max were reduced following stimulation of the cAMP pathway. Because of the inability to measure kinetic parameters for SLC activity in the rat PT cell model, only standard SLC activity could be measured and this was not affected by stimulation of cAMP pathway using cAMP derivatives or forskolin. This is the first study which has identified SLC activity in a renal cell type and further characterisation will hopefully lead to the identification of the protein responsible for SLC activity and contribute to the understanding of the pathophysiological role this transport mechanism.

No description available.

No description available.

Thesis--Copenhagen. / General summary in English and Danish. "Reprints of author's previous investigations (Papers I-VI)": [66] p. at end. Includes bibliographical references.

Thesis--Copenhagen. / General summary in English and Danish. "Reprints of author's previous investigations (Papers I-VI)": [66] p. at end. Includes bibliographical references.