Angiotensin II influences the renal hemodynamic response to blockade of thromboxane A2 and prostaglandin H2 receptors.
This study was designed to examine the influence of angiotensin II on the renal hemodynamic response to blockade of thromboxane A2 and prostaglandin H2 receptors with SQ29548 (2 mg/kg, i.v. bolus, plus 2 mg kg-1 hr-1 infusion) in anesthetized rats. In control rats without any pretreatment, SQ29548 did not change blood pressure, but increased renal blood flow from 7.0 +/- 0.4 to 7.7 +/- 0.4 ml min-1 g kidney weight-1 (P < .05) and decreased renal vascular resistance from 18.1 +/- 1.0 to 16.2 +/- 0.8 mm Hg/ml min-1 g kidney weight-1 (P < .05). In contrast, SQ29548 was without effect on renal blood flow or renal vascular resistance in rats pretreated with saralasin or captopril to block angiotensin II actions and formation, respectively. SQ29548 also increased renal blood flow and decreased renal vascular resistance in rats pretreated with captopril in which the plasma concentration of angiotensin II was fixed at elevated levels by concurrently infusing the peptide at doses ranging from 5 to 80 ng/min. In this experimental setting, the administration of SQ29548 reduced preglomerular vascular resistance selectively. Because, according to previous studies, SQ29548 does not interfere with the direct vasoconstrictor actions of angiotensin II, the renal vasodilatory effect of SQ29548 in rats with elevated plasma angiotensin II is attributable to interference with the operation of mechanisms of vasoconstriction mediated by activation of thromboxane A2-prostaglandin H2 receptors. We conclude that the status of the renin-angiotensin system is a determinant of the renal vasodilatory response to SQ29548.(ABSTRACT TRUNCATED AT 250 WORDS)
Yamaguchi
Y
Y
Department of Pharmacology, New York Medical College, Valhalla.
Fenoy
F J
FJ
Roman
R J
RJ
Nasjletti
A
A
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors*; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors*; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D012079:Renal Circulation / Q000187:drug effects*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors; D014655:Vascular Resistance / Q000187:drug effects
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D000804:Angiotensin II; D013928:Thromboxane A2; C045749:SQ 29548