Occipital artery function during the development of 2-kidney, 1-clip hypertension in the rat
Chelko, Stephen Patrick
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Renovascular hypertension (RVH) is the most common form of secondary hypertension. Decreased renal perfusion activates the renin-angiotensin-aldosterone system, increases vascular resistance as a result of angiotensin II (AII)-dependent constriction of resistance arteries, reduces the sensitivity of the baroreflex system, and increases aldosterone- and arginine vasopressin (AVP)-induced sodium and water retention. Although these aspects of RVH have been known for decades, further research is required to elucidate the precise mechanisms responsible for the development of RVH. Recently, it has been reported that blood-borne factors can gain access to the nodose ganglion exclusively by the occipital artery (OA). Since the nodose ganglion plays an important role in blood pressure homeostasis, this thesis is centered around the hypothesis that the OA may also play a similarly vital role in blood pressure regulation in health and disease. This dissertation details 1) the first characterization of the contractile responses of OA of the rat, 2) the development of a novel vascular clip designed to provide significant improvements to the most commonly-used model of RVH (2-kidney, 1-clip, 2K1C), and 3) the effects of RVH on the function of rat OA. The results of these studies are consistent with AII, AVP and 5-hydroxytryptamine (5-HT) induced OA vasoconstriction being mediated by AII1, AVP1 and 5-HT2 type receptors, respectively. Additionally, the design elements of the novel vascular clip prevented dislodgment after implantation, and produced reliable increases in blood pressure and plasma renin concentrations in 2K1C rats. In 2K1C rats, RVH-associated alterations in OA contractile function were both agonist- and segment-specific. Collectively, these studies represent the first steps to elucidating the role of the OA in blood pressure regulation in a reliable model of RVH.