Effects of L-type calcium channel activation on renal vascular resistances in the Lyon hypertensive rat.
This study aimed to evaluate the role of L-type calcium channels in the increased renal vascular resistance (RVR) of the Lyon hypertensive (LH) rat before and after normalization of its blood pressure (BP) by angiotensin-converting enzyme inhibition with perindopril. Concentration-response curves to Bay K 8644 (from 0.1 nM to 1 microM), a selective agonist of L-type calcium channels, were obtained in single-pass perfused kidneys isolated from groups of eight untreated or perindopril-treated (3 mg/kg/day, p.o., from age 3 to 7 weeks) LH and low-BP (LL) control rats. In untreated rats, the negative logarithm of the molar concentration of Bay K 8644 required to produce a half-maximal effect (pD2) values for Bay K 8644 did not differ between the two strains, whereas the maximal RVR response was higher in LH than in LL kidneys (28.0+/-4.9 vs. 12.9+/-0.8 mm Hg/ml/min/g, respectively). Perindopril normalized BP and RVR in LH rats and suppressed the interstrain differences in the maximal RVR responses (11.4+/-0.6 vs. 10.5+/-1.2 mm Hg/ml/min/g in LH and LL rats, respectively). These results demonstrate that LH rats exhibit an increased maximal contractile response to Bay K 8644 compared with LL controls, and that this alteration is not a primary defect because it disappears after normalization of BP level.
Le Roy
A L
AL
Département de Physiologie et Pharmacologie Clinique, ESA CNRS 5014, Faculté de Pharmacie, Lyon, France.
Messer-Létienne
I
I
Bernard
N
N
Benzoni
D
D
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects; D007677:Kidney Function Tests; D008297:Male; D020913:Perindopril; D051381:Rats; D014655:Vascular Resistance / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D002120:Calcium Channel Agonists; D015220:Calcium Channels; D007211:Indoles; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020913:Perindopril