All Phenotypes Cyb5r3<tm1c(KOMP)Wtsi> MGI Mouse

• heart rates are lower over a total 24 hour period in tamoxifen-induced mice

• tamoxifen-induced mice infused with angiotensin II show decreased heart rate compared to controls during the first 7 days of angiotensin treatment but while heart rate in wild-type mice declines between 8-9 days of angiotensin II, mutant mice maintain a consistent heart rate

increased susceptibility to hypertension ( J:280543 )

• mice are more susceptible to hypertensive agonists and have impaired ability to mitigate the effects of angiotensin II

increased mean systemic arterial blood pressure ( J:280543 )

• tamoxifen-induced mice exhibit a 5.84-mmHg increase in mean arterial pressure over a 24 hour period, with higher systolic and diastolic pressures

• tamoxifen-induced mice infused with angiotensin II to drive soluble guanylyl cyclase oxidation and elevate blood pressure exhibit a 14.75-mmHg blood pressure increase, with an increase in both mean arterial systolic and diastolic pressures

increased vasoconstriction ( J:280543 )

• hypertensive (via angiotensin II treatment) tamoxifen-induced mice show increased vasoconstriciton of mesenteric arteries in response to the thromboxane mimetic U46619

• however, vasoconstriction of non-angiotensin treated mesenteric arteries with U46619 shows no difference between wild-type and tamoxifen-treated mutant mice

decreased vasodilation ( J:280543 )

• tamoxifen-induced mice exhibit impaired acetylcholine-induced vasodilation in mesenteric arteries

• tamoxifen-induced mice exhibit a slight, but significant, impairment in vasodilation response of mesenteric arteries to BAY 58-2667, a soluble guanylyl cyclase heme-independent activator

• however, mice do not show differences in sodium nitroprusside, a nitric oxide donor molecule, induced vasodilation in mesenteric arteries

• tamoxifen-induced mice treated with angiotensin II to induce hypertension show impaired acetylcholine-mediated vasodilation

• hypertensive (via angiotensin II treatment) tamoxifen-induced mice exhibit diminished nitric oxide-dependent vasodilation in mesenteric arteries

• aortas from hypertensive tamoxifen-induced mice are less responsive to acetylcholine-mediated vasodilation

• however, aortas show no difference in phenylephrine-mediated vasoconstriction or vasodilation via SNP or BAY 58-2667

increased vasodilation ( J:280543 )

• hypertensive tamoxifen-induced mice exhibit increased vasodilation responsiveness to soluble guanylyl cyclase heme-independent activator BAY 58-2667

increased physiological sensitivity to xenobiotic ( J:280543 )

• acute injection of BAY 58-2667 in angiotensin II-treated hypertensive tamoxifen-induced mice results in a greater blood pressure reduction than in controls

decreased monocyte cell number ( J:280543 )

• tamoxifen-induced mice exhibit fewer circulating monocytes compared to wild-type mice

• however, white blood cell, red blood cell, platelet, lymphocyte, and granulocyte counts are normal and hematocrit and hemoglobin levels are normal