Mesenteric cyclooxygenase products after combined antihypertensive treatment in uninephrectomized SHRs.
Unilateral nephrectomy in the spontaneously hypertensive rat (SHR) does not produce any change in blood pressure but does induce humoral alterations that might influence the antihypertensive action of some drugs. In this study, the antihypertensive effect of treatment (5 weeks) with placebo (control), verapamil, trandolapril, or their combination (verapamil plus trandolapril) was investigated in SHRs with half renal mass ablation, regarding the structure and function of small mesenteric arteries. Arterial pressure was followed during the period of treatment. Trandolapril and veratran returned pressure to normal, while verapamil was ineffective. Statistically significant differences in the parameters of vessel structure were not observed among groups; thus, the alterations in functionality cannot be attributed to morphologic changes. The noradrenaline-induced contraction was reduced similarly by the three treatments as compared to controls. This difference involved a higher participation of nitric oxide in the trandolapril group, while in the verapamil group the origin of the difference might be due to the abolishment of a cyclooxygenase product. Veratran retained both effects. Acetylcholine-evoked relaxation of vessels precontracted with noradrenaline was improved with treatments versus controls. The abolishment of a contracting prostanoid or an NO scavenger from the cyclooxygenase pathway, due to the treatments implemented, is probably the cause of this.
López-Hernández
F J
FJ
Departamento de Fisiología y Farmacología, Facultad de Farmacia, Universidad de Salamanca, Spain.
Montero
M J
MJ
Carrón
R
R
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology*; D007211:Indoles / Q000627:therapeutic use; D007213:Indomethacin / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000201:enzymology*; D009200:Myocardial Contraction / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009392:Nephrectomy; D009569:Nitric Oxide / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D014700:Verapamil / Q000627:therapeutic use
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril; D009569:Nitric Oxide; D014700:Verapamil; D011451:Prostaglandin-Endoperoxide Synthases; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin