Pharmacokinetic changes induced by vasomodulators in kidneys, livers, muscles, and implanted tumors in rats as measured by dynamic Gd-DTPA-enhanced MRI.
The effects of three physiologically different vasomodulators, angiotensin II (a vasoconstrictor), hydralazine (a vasodilator), and histamine (a permeability modulator), on the pharmaco-kinetics of entry of small molecules (measured by Gd-DTPA concentration) into normal and abnormal tissue were studied in rats implanted with R3230 AC tumors. Sequential dynamic Gd-DTPA-enhanced MRI studies, one before and one after vasomodulator administration, were performed, and the signal intensities of various tissues analyzed. Angiotensin II (6 micrograms/kg) reduced blood flow in tumors, but increased it in muscles. Hydralazine (5 mg/kg) reduced blood flow in tumors, kidneys, and livers, and slowed Gd-DTPA clearance from tumors, livers, and muscles. Histamine (25 micrograms/kg) increased renal blood flow, hastening Gd-DTPA clearance causing reduced measurable blood flow in tumors and muscles. By simultaneously monitoring the effects in various tissues, the pharmacokinetic effect of each drug in the entire body could be obtained.
Su
M Y
MY
Department of Radiological Sciences, University of California, Irvine 92714, USA.
Wang
Z
Z
Roth
G M
GM
Lao
X
X
Samoszuk
M K
MK
Nalcioglu
O
O
D000230:Adenocarcinoma / Q000378:metabolism* / Q000503:physiopathology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D002199:Capillary Permeability; D017690:Cell Transplantation; D003287:Contrast Media / Q000493:pharmacokinetics; D005260:Female; D019786:Gadolinium DTPA; D006830:Hydralazine / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D018810:Magnetic Resonance Angiography / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008325:Mammary Neoplasms, Experimental / Q000378:metabolism* / Q000503:physiopathology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D004369:Pentetic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D051381:Rats; D011916:Rats, Inbred F344; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D003287:Contrast Media; D009942:Organometallic Compounds; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D006830:Hydralazine; D004369:Pentetic Acid; D019786:Gadolinium DTPA