Endothelium-derived relaxing factor, hypertension and chronic parathyroidectomy in spontaneously hypertensive and Wistar-Kyoto rats.
1. Parathyroidectomy (PTX) lessens the development of hypertension in young spontaneously hypertensive rats (SHR) and the involved mechanisms remain to be elucidated. We have studied here the aortic vascular reactivity to both norepinephrine (NE) and acetylcholine in 10 week old male PTX SHR and Wistar-Kyoto (WKY) rats. 2. Depolarized (KCl 100 mmol/L) and NE (1 mumol/L or cumulative 10(-9)-10(-5) mol/L) precontracted intact aortic rings from PTX rats show a significant and unexpected increase of maximal contractile responses in normotensive and hypertensive animals. These results are also obtained with low extracellular ionized calcium levels (0.625 and 0.9 mmol/L) similar to PTX ionized plasma calcium. N omega-Nitro-L-arginine methyl ester (L-NAME, 20 mumol/L) potentiates the NE response in SHR and WKY rats, more significantly in control than in PTX animals. 3. In the presence of indomethacin (10 mumol/L) in SHR the potentiating effect of PTX on NE contraction is still observed, ruling out a specific production of vasoconstrictors from the arachidonic cascade by the PTX rat aortic endothelium. 4. After PTX a moderate impairment of acetylcholine relaxant responses is observed in SHR and WKY rat aortas and basal aortic cyclic guanosine 3'-5' monophosphate (cGMP) content is also decreased; nevertheless sodium nitroprusside causes a similar relaxation. Furthermore in L-NAME-treated aortas and in the presence of L-arginine (100 mumol/L), acetylcholine (1 mumol/L) produces a significantly less pronounced relaxation in PTX rats. 5. In conclusion, the enhancement of NE contractile response in PTX rat aortas is not linked to the strain but probably related to a decrease in endothelial nitric oxide (NO) release or activity. Enhancement of force generation that we describe does not directly participate in the attenuated hypertension observed in SHR after parathyroidectomy.
Boulebda
N
N
Pharmacologie Cellulaire et Moléculaire, CNRS UA 600, Faculté de Pharmacie, Université Louis Pasteur, Strasbourg, France.
Van Overloop
B
B
Gairard
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D006152:Cyclic GMP / Q000097:blood; D004347:Drug Interactions; D005110:Extracellular Space / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology* / Q000517:prevention & control* / Q000601:surgery; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010280:Parathyroid Glands / Q000502:physiology* / Q000601:surgery; D016105:Parathyroidectomy; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D009599:Nitroprusside; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP; D000109:Acetylcholine; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin