Adenosine modulates vasomotor tone in outer medullary descending vasa recta of the rat.
Adenosine is generated within the renal medulla under hypoxic conditions and is known to induce net vasoconstriction within the renal cortex while increasing medullary blood flow and oxygenation. To test the hypothesis that vasoconstriction of outer medullary descending vasa recta (OMDVR) is modulated by adenosine, we examined the effects of adenosine and adenosine Al and A2 receptor subtype agonists on in vitro perfused control and preconstricted rat OMDVR. Constriction with angiotensin II (ANG II, 10(-9) M) was attenuated by adenosine in a concentration-dependent manner (EC50 = 2.0 x 10(-7)M, P < 0.05). Similarly, an adenosine A2 agonist (CGS-21680, 10(-7) M), but not an adenosine Al agonist (cyclohexyladenosine, 10(-6) M), attenuated ANG II-induced vasoconstriction. Under control conditions, ablumenal application of adenosine (10(-12) to 10(-5) M) elicited a biphasic response. Additionally, cyclohexyladenosine (10(-6) M) caused vasoconstriction and CGS-21680 (10(-6) M) had no effect on untreated vessels. Finally, an influence of ANG II receptor stimulation on adenosine Al receptor-mediated vasoconstriction could not be shown. These data suggest that OMDVR possess both Al and A2 adenosine receptors and that they mediate constriction and dilatation, respectively. We conclude that adenosine is a potent modulator of OMDVR vasomotor tone and that its net effect is dependent upon local concentrations.
Silldorff
E P
EP
Department of Medicine, Division of Nephrology, Pennsylvania State University, Hershey Medical Center, Hershey 17033, USA.
Kreisberg
M S
MS
Pallone
T L
TL
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects*; D009129:Muscle Tonus / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; C027513:N(6)-cyclohexyladenosine; D000241:Adenosine