STUDIES ON UPTAKE AND CATABOLISM OF VASCULAR HISTAMINE IN SPONTANEOUSLY HYPERTENSIVE RATS

Abstract

Reduced vascular histamine content is postulated to contribute to increased peripheral vascular resistance in experimental hypertension in rats. Experiments were conducted to examine histamine content, in vitro uptake ability and in vitro catabolism of histamine in blood vessels from 12-wk-old spontaneously hypertensive rats (SHR) and age-matched normotensive controls. Histamine content of mesenteric artery and abdominal aorta from SHR was significantly reduced (P < 0.05) when compared to Wistar-Kyoto normotensive controls. This finding confirms a similar observation of reduced vascular histamine content in deoxycorticosterone acetate salt hypertensive rats reported previously. This reduction in histamine content may be more prevalent in arteries because the decrease was not observed in the portal vein from SHR. Uptake of [14C]histamine into mesenteric artery and abdominal aorta was unchanged in SHR compared to Wistar-Kyoto controls. No significant differences between slopes for uptake regression lines were observed for either mesenteric artery or abdominal aorta. Mesenteric artery exhibited a greater capacity of [14C]histamine accumulation than aorta and significant reductions in accumulation of labeled histamine after 20 and 60 min were found in this vessel from SHR. Because metabolism of histamine was inhibited by aminoguanidine, this reduction may reflect diminished retention by histamine storage sites. In vitro 1-[14C]histidine uptake was significantly increased in abdominal aorta and iliac artery but not mesenteric artery from SHR. These differences were also present at the later accumulation periods of 20 and 60 min. When histamine catabolism was examined, the major vascular metabolite of histamine, imidazoleacetic acid, was present in significantly greater (P < 0.05) amounts in abdominal aorta and iliac artery from SHR compared to Wistar-Kyoto controls. This increase in [14C]imidazoleacetic acid was accompanied by a decrease in [14C]histamine present. Reduced vascular histamine may contribute to elevated vascular resistance seen in SHR at 12 weeks of age. The reduction in vascular histamine content in the SHR may be related, in part, to an enhanced conversion of histamine to imidazoleacetic acid and not to a reduced uptake rate for histamine. Differences in L-histidine uptake may reflect a compensatory response to the reduced histamine content in the vessels examined.