The effects of blood pressure variation on vascular structure and function in genetic and experimental hypertension.
thesisposted on 2015-11-19, 08:51 authored by S. J. Bund
It is widely believed that vascular smooth muscle in spontaneously hypertensive rats (SHR) is prone to a greater genetically determined propensity to growth because antihypertensive drugs typically do not completely normalise the structural development of SHR resistance arteries. In order to investigate this further, the blood pressure rise in one hindlimb of SHR and normotensive Wistar Kyoto (WKY) control rats was attenuated by a partially constricting ligature around one external iliac artery at 5 weeks. Therefore blood pressure reduction was mediated by non-therapeutic means. At 12 and 24 weeks the femoral mean arterial pressure distal to the ligature was reduced in both strains, and the low pressure hindlimb in the SHR was subject to perfusion pressures similar to normally perfused WKY hindlimbs. Femoral resistance arteries were mounted in a myograph to permit measurements of morphology and reactivity. The smooth muscle content of arteries distal to the ligature was reduced in both strains and SHR arteries from the low pressure hindlimb were structurally indistinguishable from those of normally perfused WKY hindlimbs, suggesting that blood pressure was the major determinant of vascular structure and SHR femoral vascular smooth muscle is not subject to greater pressure independent influences. The reduced noradrenaline sensitivity in SHR arteries at 12 and 24 weeks was normalised distal to the ligature in 12 week rats. Noradrenaline-stimulated calcium sensitivity was increased only at 12 weeks but the ligature increased this sensitivity at both ages in SHR. The ligature did not influence noradrenaline or noradrenaline-stimulated calcium sensitivity in WKY rats. Additional studies revealed that vasopressin sensitivity is normal in SHR mesenteric resistance arteries but vasopressin-stimulated calcium sensitivity is increased. Also, mesenteric resistance arteries from Wistar rats made hypertensive by 2-bromoethylamine-induced chemical renal medullectomy have reduced noradrenaline sensitivities - a possible mechanism for reduced pressor responses to noradrenaline in vivo.
Date of award1990-01-01
Author affiliationCollege of Medicine, Biological Sciences and Psychology
Awarding institutionUniversity of Leicester