Different vascular responsiveness to angiotensin II in two normotensive rat strains.
Rats of the Fischer 344 (F344) and Wistar Kyoto (WKY) strains are known to present differences in stimuli responses involving the renin-angiotensin system and in cardiovascular responses to an acoustic startle stimulus. Here we compared the vascular reactivity to angiotensin II (ANG II) of these normotensive, inbred rat strains. Blood pressure (BP) and heart rate (HR) were recorded in conscious rats, before and after a neurohumoral blockade obtained by successive administration of chlorisondamine, enalapril, a V1-vasopressinergic receptor antagonist (Manning compound) and atropine methyl nitrate. BP was restored by a constant infusion of noradrenaline. Boluses of ANG II ranging from 0.001 to 1280 ng/kg were injected randomly. Average dose-response curves were established. After neurohumoral blockade, the minimum mean BP (MBP) produced by hydralazine (3 mg/kg, i.v.) and the maximum MBP produced by noradrenaline (60 microg/mL and 800 microL/min, i.v.) were used to reflect arterial wall structure. The maximal systolic blood pressure (SBP) and pulse pressure (PP) responses to ANG II were higher in F344 compared with WKY (+86 +/- 3 mmHg vs. +71 +/- 3 mmHg, P < 0.01 for SBP, +31 +/- 2 mmHg vs. +18 +/- 1 mmHg, P < 0.001 for PP). After the ANG II type 1 (AT1) receptor blocker valsartan, ANG II had no significant effect on BP. F344 and WKY exhibited the same maximum MBP in response to noradrenaline. However, MBP level following hydralazine was higher in F344 (F344: 48 +/- 2 mmHg vs. WKY: 37 +/- 3 mmHg, P < 0.01). The amplification in F344 of the vasoconstrictive response to ANG II mediated by AT1 receptors is compatible with a high number of AT1 receptors in this strain. In F344, the exaggerated systolic and PP responses to ANG II and the higher MBP level after hydralazine most likely reflect a structural modification of the arterial wall such as hypertrophic remodelling in F344.
Herin
Laetitia
L
INSERM E0107, Laboratoire de Biomécanique et Pharmacologie de la Paroi Artérielle, 15, rue de l'Ecole de médecine, 75270 Paris Cedex 06, France. laetitia.herin@bhdc.jussieu.fr
Blanc
Jocelyne
J
Basset
Alexandra
A
Laude
Dominique
D
Laurent
Stéphane
S
Elghozi
Jean-Luc
JL
D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II