EFLORNITHINE TREATMENT IN SHR - POTENTIAL ROLE OF VASCULAR POLYAMINESAND ORNITHINE DECARBOXYLASE IN HYPERTENSION

This study was performed to assess the potential role of polyamines in the alterations in vascular structure and function in spontaneously h ypertensive rats (SHR). The effects of chronic administration of eflor nithine (alpha-difluoromethylornithine; DFMO), a highly specific inhib itor of ornithine decarboxylase (the rate limiting enzyme in polyamine biosynthesis), on vascular polyamine contents, vascular structure and function, and blood pressure was studied. Male SHR (16-17 weeks of ag e) with an average systolic blood pressure (Ssp) of 161 +/- 3 mmHg wer e used. The rats were divided into two groups and received either tap water or a 1% DFMO solution to drink for 6 weeks. SBP and body weight were recorded prior to and once-a-week during the experiment. Standard in vitro vascular reactivity studies on ring segments of aorta and ta il artery were performed. Ring segment weight, arterial medial thickne ss, and vascular polyamine contents were also determined. Body weights were not significantly affected by the DFMO treatment. SBP in control SHR rose progressively to an average value of 185 +/- 5 mmHg by the s ixth experimental week. Although DFMO treatment did not cause a signif icant decrease in SBP compared to pretreatment values, it did prevent a further increase in SBP. Aortic and tail artery responsiveness to no repinephrine and electrical stimulation, respectively, ring segment we ight, arterial medial thickness, and vascular polyamine contents were all significantly less in SHR receiving the DFMO treatment. These data are the first to demonstrate the effectiveness of DFMO to lower polya mine contents in the vasculature of hypertensive SHR. Importantly, chr onic DFMO treatment prevented the further rise in SBP as well as the c hanges in vascular structure and function associated with the elevatio n in blood pressure. Thus, it appears that polyamines may play an impo rtant role in mediating the vascular alterations in SHR.