Sensitivity and Reactivity to Endothelin-1 in Mesenteric Beds and Aortic Rings of 4-Week-Old Spontaneously Hypertensive Rats

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Abstract
The vasoconstrictor effects of endothelin-1 were studied in perfused mesenteric vascular beds (MVB) and aortic rings of 4-week-old spontaneously hypertensive rats (SHR) and age-matched Wistar Kyoto rats (WKY). Mean blood pressure (124 +/- 4 vs. 97 +/- 3 mmHg) and initial perfusion pressure in the MVBs (25 +/- 2 vs. 19.7 +/- 1.2) were significantly higher in SHR. Reactivity to endothelin-1 was increased in MVBs of SHR, as indicated by the maximum perfusion pressure obtained (223 +/- 8 vs 155 +/- 7 mmHg, p less than 0.001), whereas there was no significant difference in sensitivity between the two strains (EC50 values: 50 +/- 12 and 80 +/- 15 pmol, respectively). By contrast, in aortic rings reactivity and sensitivity to endothelin-1 were similar in both strains, (EC50s: 1.8 +/- 0.12 and 1.4 +/- 0.1 nM). Reactivity to norepinephrine was increased in MVBs, but reduced in aortic rings of SHR. The unchanged sensitivity to endothelin-1 and the unspecifically increased reactivity in the MVBs of SHR to endothelin-1 and norepinephrine indicate rather a change in vascular structure and not a functional abnormality. These results suggest that hyperreactivity to endothelin-1 may not be a primary hypertensive mechanism in genetic hypertension.