Effect of ouabain in pressurized middle cerebral arteries from normotensive and hypertensive rats.
The aim of the present study was to assess the ability of ouabain to induce vasomotor responses and interfere with the myogenic tone in isolated segments of middle cerebral arteries from male Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) subjected to different pressures and no-flow conditions using a pressure myograph. At 60 mmHg, ouabain (1 nM-1 mM) caused relaxations at concentrations of 10 microM and up in segments from WKY while 1 nM ouabain produced a relaxation that was unaltered by the remaining concentrations in SHR segments. The relaxations were higher in SHR than in WKY arteries. Endothelium removal practically abolished the relaxation in arteries from both strains, whereas 10 microM L-NAME (an inhibitor of nitric oxide synthase) had no effect. When arteries were pressurized from 20-120 mmHg, myogenic activity developed in 3 out of 10 WKY arteries while SHR arteries did not show myogenic tone. Endothelium removal did not alter the effects of pressure increase in both strains, and incubation of segments in a Ca(2+)-free medium to abolish myogenic tone, shifted the pressure-response curve of WKY segments to the left; pressure-response curves from SHR were not modified. Although ouabain (0.1 mM) did not alter the pressure-response curve from WKY segments, curves obtained from SHR were shifted to the left. These results suggest that: 1) ouabain produces vasodilation in pressurized middle cerebral arteries of WKY and SHR which is positively modulated by an endothelial factor distinct from nitric oxide; and 2) only WKY arteries develop myogenic activity while the diameter of SHR arteries is passively enhanced with increases in intraluminal pressure. This passive increase is facilitated by ouabain. Therefore, hypertension modifies the mechanical properties of cerebral arteries resulting in a loss in the capacity for autoregulation.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014664:Vasodilation / Q000187:drug effects*