Gomez-Alamillo Carlos, Juncos Luis A, Cases Aleix, Haas John A, Romero J Carlos
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minn 55905, USA.
Hypertension. 2003 Oct;42(4):831-6. doi: 10.1161/01.HYP.0000088854.04562.DA. Epub 2003 Aug 18.
We examined whether interactions between angiotensin II (Ang II), endothelin (ET), nitric oxide (NO), and prostaglandins (PGs) differentially regulate perfusion to distinct vascular beds. For this, we blocked either angiotensin AT1 or ET receptors or both and then sequentially inhibited NO and PG synthesis in anesthetized dogs. Blocking Ang II or ET had similar effects on systemic hemodynamics: Mean arterial pressure fell slightly without altering cardiac output. Blocking both caused a synergistic fall in mean arterial pressure and increased cardiac output. Pulmonary vascular resistance was not altered by blocking Ang II, ET, or both but progressively increased during NO and PG blockade in group 2 (which had unblocked ET receptors), suggesting that endogenous ET exerts pulmonary vasoconstriction that is tempered by NO and PGs. In the kidney, blocking Ang II increased regional blood flow (RBF), glomerular filtration rate (GFR), and fractional excretion of sodium (FENa). In contrast, blocking ET did not alter RBF, and it decreased GFR and FENa. Combined Ang II and ET blockade markedly increased RBF without altering GFR, and FENa was maintained at the levels as when only ET was blocked. Sequentially inhibiting NO and PGs decreased RBF when Ang II or ET were blocked but had little effect when both were blocked. Finally, Ang II or ET blockade did not alter iliac blood flow. Inhibiting NO and PGs decreased iliac blood flow when Ang II or ET but not both were blocked. These results suggest that regional differences in the interactions between endogenous Ang II, ET, NO, and PGs are important determinants in systemic, pulmonary, and regional hemodynamics.
我们研究了血管紧张素II（Ang II）、内皮素（ET）、一氧化氮（NO）和前列腺素（PGs）之间的相互作用是否对不同血管床的灌注有不同的调节作用。为此，我们阻断血管紧张素AT1受体或ET受体，或两者都阻断，然后在麻醉犬中依次抑制NO和PG的合成。阻断Ang II或ET对全身血流动力学有相似的影响：平均动脉压略有下降，而心输出量未改变。同时阻断两者会导致平均动脉压协同下降，并增加心输出量。阻断Ang II、ET或两者对肺血管阻力均无影响，但在第2组（ET受体未阻断）中，在NO和PG阻断过程中肺血管阻力逐渐增加，这表明内源性ET发挥肺血管收缩作用，而NO和PG可对其进行调节。在肾脏中，阻断Ang II可增加肾血流量（RBF）、肾小球滤过率（GFR）和钠排泄分数（FENa）。相反，阻断ET不会改变RBF，但会降低GFR和FENa。联合阻断Ang II和ET可显著增加RBF，而不改变GFR，FENa维持在仅阻断ET时的水平。当阻断Ang II或ET时，依次抑制NO和PG会降低RBF，但当两者都阻断时影响较小。最后，阻断Ang II或ET不会改变髂血流量。当仅阻断Ang II或ET（而非两者都阻断）时，抑制NO和PG会降低髂血流量。这些结果表明，内源性Ang II、ET、NO和PG之间相互作用的区域差异是全身、肺和局部血流动力学的重要决定因素。
