Young, genetically hypertensive Lyon (LH) rats exhibited an increased renal in vivo turnover of norepinephrine and an elevated urinary excretion of thromboxane B 2 when compared with nonnotensive (LN) and low blood pressure (LL) controls. Therefore, the effects of norepinephrine (1.2 xlO" 8 to 9.6 xlO" 7 M) and of phenylephrine (5xlO~8 to 1.9x10"' M) on renal function and the urinary excretion of prostanoids were assessed in isolated perfused kidneys of 8-week-old LH, LN, and LL rats. In addition, the effects of norepinephrine were assessed before and during thromboxane A 2 /prostaglandin H 2 receptor blockade by AH23848 (4xlO~* M). Before drug infusion, LH kidneys differed from those of LN and LL controls by having an elevated renal vascular resistance and a decreased natriuresis and glomerular filtration rate; the urinary output of prostaglandin E 2 and F^, of 6-ketoprostaglandin F la , and of thromboxane B 2 was similar in the three strains. The constrictor effects of norepinephrine and phenylephrine were significantly increased in LH rat kidneys compared with LL but not with LN controls, and their pressure-natriuresis was markedly reduced. Norepinephrine and phenylephrine induced a 10-to 20-fold dose-dependent increase in the synthesis of the four prostanoids, which was more pronounced in LH than in LN and LL rats for thromboxane B 2 only. AH23848 infusion significantly reduced the vascular effects of norepinephrine and increased the natriuretic response of LH but not of LN and LL rat kidneys. In conclusion, isolated perfused kidneys from LH rats exhibit an increased production of thromboxane A 2 , which enhances the renal effects of norepinephrine and therefore could participate in the development of hypertension of the Lyon model. (Hypertension 1991;17:296-302)

The present work demonstrates that LH rats are salt sensitive. This characteristic manifests despite the lack of an active renin-angiotensin system and is not explained by a hypersensitivity to aldosterone.

The present study evaluated the acute effects of ANG II (5-480 ng/kg iv) and phenylephrine (PE; 0.2-146 microg/kg iv) on total renal (RBF) and medullary blood flow (MBF) in anesthetized Lyon hypertensive (LH) and low-blood-pressure (LL) rats. ANG II and PE induced dose-dependent decreases in both RBF and MBF, which were greater in LH than in LL rats. Interestingly, after ANG II, but not after PE, the initial medullary vasoconstriction was followed by a long-lasting and dose-dependent vasodilation that was significantly blunted in LH compared with LL rats. The mechanisms of the MBF effects of ANG II were studied in LL rats only. Blockade of AT(1) receptors with losartan (10 mg/kg) abolished all the effects of ANG II, whereas AT(2) receptor blockade with PD-123319 (50 microg x kg(-1) x min(-1) iv) did not change these effects. Indomethacin (5 mg/kg) decreased by approximately 90% the medullary vasodilation induced by the lowest doses of ANG II (from 15 ng/kg). In contrast, N(G)-nitro-l-arginine methyl ester (10 mg/kg and 0.1 mg. kg(-1). min(-1) iv) and the bradykinin B(2)-receptor antagonist HOE-140 (20 microg/kg and 10 microg x kg(-1) x min(-1) iv) markedly lowered the medullary vasodilation at the highest doses of ANG II only. In conclusion, this study shows that LH rats exhibit an altered MBF response to ANG II compared with LL rats and indicates that the AT(1) receptor-mediated medullary vasodilator response to low doses of ANG II is mainly due to the release of PGs, whereas the dilator response to high doses of ANG II has additional nitric oxide- and kinin-dependent components.

Objective: This study evaluated the consequences of thyroid hormone receptor-E (TRE) disruption on vascular reactivity. Methods: The activity of superior mesenteric arteries isolated from TRE knockout mice generated in the SV129 background (TRE^0/0SV) or in a pure C57BL/6 background (TRE^0/0C57) was compared to that of their corresponding wild-type strains (SV129 or C57BL/6 mice). Results: The wild-type SV129 mice exhibited an impaired acetylcholine (Ach)-induced mesenteric artery relaxationcompared to C57BL/6 mice, associated with greater responses to angiotensin II (AII) and phenylephrine (PE). The disruption of TRE decreased the vascular response to sodium nitroprusside and PE in both the SV129 and C57BL/6 genetic backgrounds.Responses to Ach and AII were also blunted, but only in TRE^0/0C57 mice. The administration of 3,3′5-triiodo-L-thyronine sodium salt (T₃) elicited a vasodilatation in C57BL/6 mice even at the lowest concentration (10^-9M); a maximal relaxation of more than 50% was observed with the concentrations between 10^-9 and 10^-8M. However, the response to T₃ was nearly absent in TRE^0/0C57 mice. Conclusion: TRE is essential for the control of vascular tone, particularly in thyroid hormone-mediated relaxation. The difference in response to Ach observed between the two wild-type mice should be taken into account for interpreting the vascular responses of genetically engineered mice. i 2014 S. Karger AG, Basel