Role of nitric oxyde in modulation of regionally different vascular responses in mesenteric vascular bed

Pl-15 ROLE OF NITRIC OXYDE IN MODULATION OF REGIONALLY DIFFERENT VASCULAR RESPONSES IN MESENTERIC VASCULAR BED L. A. Szirmai l, E. Monos 1, W. J. Stekiel 2, and J. H. Lombard 2. IExp. Res. Dept. - 2nd Inst. of Physiol., Semmelweis University of Medicine, Budapest, Hungary and 2Dept. of Physiol., Medical College of Wisconsin, Milwaukee, USA. The goal of this study was to characterize vascular responses of mesenteric resistance arteries a) in different regions along the small intestine; b) at various levels of transmurai pressure (TMP), and c) with or without inhibition of endothelial functions. Concentration-response curves to norepinephrine (NE) were obtained in resistance arteries (250-450 lttm) isolated from proximal (duodenal) and mid-intestinal (jejunal) loops of anesthetized Sprague-Dawley rats at various levels (60 mmHg, 100 mmHg and 140 mmHg) of transmural pressure using in vitro on-line videomicroscopic method. Regional differences in adrenergic constrictor sensitivity were found: jejunal arteries proved to be more sensitive to NE than duodenal ones at all the three pressure levels studied. The initial diameter was identical in the two groups, but the amplitude of maximal contraction was larger in the jejunal vs. the duodenal arteries. Passive geometrical and elastic properties were identical in the two groups. In contrast to renal arteries (Lombard et al, 1990), elevation of transmural pressure from 60 to 100 or 140 mmHg decreased the sensitivity of both types of mesenteric arteries to NE. The amplitude of contraction decreased at 140 mmHg in duodenal, but remained unchanged in jejunal arteries. Prazosin blocked the contraction, while selective alpha-2 agonists (UK14,304, B-Ht920) did not induce constriction. Mechanical deendothelisation by intravascular perfusion of air increased the sensitivity but not maximal constriction of duodenal arteries and did not affect the jejunal ones. Inhibition of cyclooxigenase products by 1 IxM indomethacin did not change the responses to NE in either vessel type. NO-blockade with 10 I.tM NG-L-nitro-arginine (L-NA) lowered the EC50 values for NE and increased the maximal constriction in the duodenal arteries but not in the jejunal ones. Neither duodenal nor jejunal arteries exhibited significant resting or pressure-induced myogenic tone, which were unaffected by L-NA treatment. Our main finding is that regional differences in vascular reactivity exist between duodenal and jejunal resistance arteries to adrenergic constrictor stimulus, and NE-induced NO-release present only in duodenal arteries is responsible for these differences. (Supported by NSF-MTA INT-8908904, USA-Hungary, ETT 6-188/1990 Hungary, NIH #HL-29587 and #HL-37374 USA)

P1-16 MORPHOLOGICAL CHANGES OF HEARTS IN STREPTOZOTOCIN-INDUCED HYPERTENSIVE RATS J. K. Seong, S. K. Do, H. K. JJn, Y. S. Oh Experimental Animal Center, Hallym University, Korea

DIABETIC SPONTANEOUSLY

Both Hypertension and diabetes are known to contribute to morbidity and mortality of cadiovascular disease(Cerielio et al, 1993). Epidemiological studies have indicated that hypertension occurs more frequently in patients with diabetes mellitus than in nondiabetic subjects. There have been reported a few animal models for diabetes metlitus associated with hypertension. Diabetes mellitus induced by streptozotocin(STZ) in adult spontaneously hypertensive rats(SHR) have hypotensive effect(Sato et al. 1991). We investigated this phenomenon further as compared with the blood pressure, heart rates, blood glucose levels and cardiac mophology in SHR, WKY and STZ-SHR. Insulin dependent diabetes mellitus was induced with streptozotocin(6Omg/Kg) at 8 weeks of age in SHR. We measured body weights, changes of systolic and diastolic blood pressure, heart rates and blood glucose levels every two weeks for 3 months. We observed myocardial alterations with Masson trichrome, PAS staining and electron microscope. We measured myocardial wall areas and left ventricular lumen areas by use of computer image analyzer. Body weights of STZ-SHR were decreased. Blood glucose levels of STZ-SHR were rapidly increased up to 600mg/dl. The systolic and diastolic blood pressure, heart rates of STZ-SHR were decreased than those of SHR. By contrast systolic and diastolic blood pressure of SHR were subecanQuently increased with aging. Left ventricular lumens of SHR were reduced due to concentric myocardial hypartrobhy. STZ-SHR showed PAS positive materials and fibrosis, mild myocardial degeneration in vetricular walls. Mitochondrial swelling, loss of myocardial fibers were observed in left ventricular wall of STZ-SHR with electron microscopical observations. By use of image analyzer, SHR showed increased myocardial wall areas and decreased ventricular lumenal areas compared with WKY. By contrast STZ-SHR showed decreased myocardial well areas and increased left ventricular lumenal areas with computer image analyzer. These results suggested that decreased blood pressure in STZ-SHR was possibly due to histological changes in hearts.

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