Interactions between vasoconstrictors and vasodilators in regulating hemodynamics of distinct vascular beds.
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.
Gomez-Alamillo
Carlos
C
Department of Physiology and Biophysics, Mayo Clinic, Rochester, Minn 55905, USA.
Juncos
Luis A
LA
Cases
Aleix
A
Haas
John A
JA
Romero
J Carlos
JC
D000804:Angiotensin II / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000077300:Bosentan; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007083:Iliac Artery / Q000187:drug effects / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1; D012039:Regional Blood Flow / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013449:Sulfonamides / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D044140:Receptor, Angiotensin, Type 1; D013449:Sulfonamides; D000804:Angiotensin II; D009569:Nitric Oxide; D008469:Meclofenamic Acid; D012964:Sodium; D019001:Nitric Oxide Synthase; D000077300:Bosentan; D019331:NG-Nitroarginine Methyl Ester