We conclude that the VPR tail-cuff method provides accurate blood pressure measurements over the physiological range of blood pressure in mice.

We rescued the embryonic lethality of global PPARγ knockout by breeding Mox2-Cre (MORE) mice with floxed PPARγ mice to inactivate PPARγ in the embryo but not in trophoblasts and created a generalized PPARγ knockout mouse model, MORE-PPARγ knockout (MORE-PGKO) mice. PPARγ inactivation caused severe lipodystrophy and insulin resistance; surprisingly, it also caused hypotension. Paradoxically, PPARγ agonists had the same effect. We showed that another mouse model of lipodystrophy was hypertensive, ruling out the lipodystrophy as a cause. Further, high salt loading did not correct the hypotension in MORE-PGKO mice. In vitro studies showed that the vasculature from MORE-PGKO mice was more sensitive to endothelial-dependent relaxation caused by muscarinic stimulation, but was not associated with changes in eNOS expression or phosphorylation. In addition, vascular smooth muscle had impaired contraction in response to α-adrenergic agents. The renin-angiotensin-aldosterone system was mildly activated, consistent with increased vascular capacitance or decreased volume. These effects are likely mechanisms contributing to the hypotension. Our results demonstrated that PPARγ is required to maintain normal adiposity and insulin sensitivity in adult mice. Surprisingly, genetic loss of PPARγ function, like activation by agonists, lowered blood pressure, likely through a mechanism involving increased vascular relaxation.

Radiotelemetry of mouse blood pressure accurately monitors systolic pressure, diastolic pressure, heart rate, and locomotor activity but requires surgical implantation. Noninvasive measurements of indirect systolic blood pressure have long been available for larger rodents and now are being reported more frequently for mice. This study compared mouse systolic arterial blood pressure measurements using implanted radiotelemetry pressure transducer with simultaneous tail-cuff measurements in the same unanesthetized mice. The pressure range for comparison was extended by inducing experimental hypertension or by observations of circadian elevations between 3 AM and 6 AM. Both trained and untrained tail-cuff operators used both instruments. Every effort was made to follow recommended manufacturer's instructions. With the initial flow-based tail-cuff instrument, we made 671 comparisons (89 sessions) and found the slope of the linear regression to be 0.118, suggesting poor agreement. In an independent assessment, 277 comparisons (35 sessions) of radiotelemetry measurements with the pulse based tail-cuff instrument were made. The slope of the linear regression of the simultaneous measurements of systolic pressures was 0.98, suggesting agreement. Bland-Altman analysis also supported our interpretation of the linear regression. Thus although reliable systolic pressure measurements are possible with either tail-cuff or radiotelemetry techniques, in our hands some tail-cuff instruments fail to accurately detect elevated blood pressures. These data, however, do not distinguish whether this instrument-specific tail-cuff failure was due to operator or instrument inadequacies. We strongly advise investigators to obtain an independent and simultaneous validation of tail-cuff determinations of mouse blood pressure before making critical genotyping determinations.

This study investigated the effects of normoxic (FIO2 = 0.21), hyperoxic (FIO2 = 1.0), and hyperoxic (FIO2 = 1.0) plus antioxidant pretreatment (tirilazad mesylate) [corrected] resuscitation on neurologic outcome following 9 min of normothermic (39 +/- 1.0 degrees C) cardiac arrest. Physiologic variables including arterial blood gases and neurologic outcome, which was assessed using a standardized scoring system, were followed over a 24-h period following resuscitation from cardiac arrest. Hyperoxically resuscitated dogs sustained significantly worse neurological deficit at 12 and 24 h (mean scores: 39 +/- 3 and 49 +/- 8, respectively) than did antioxidant pretreated hyperoxically resuscitated dogs (mean scores: 22 +/- 1, P = 0.0007 and 22 +/- 1, P = 0.004, respectively) and normoxically resuscitated dogs (mean scores: 28 +/- 4, P = 0.025 and 33 +/- 8, P = 0.041 respectively). These data suggest that oxidant injury has a major role in central nervous system dysfunction following successful resuscitation from 9 min of cardiac arrest. Also, resuscitation from cardiac arrest with hyperoxic FIO2's may contribute to and further exacerbate neurologic dysfunction.

Background: Protoporphyria causes mouse liver damage in association with lamin aggregation. Results: Endogenously and exogenously stimulated protoporphyrin-IX accumulation leads to ambient light-triggered organelle-selective protein aggregation, ultrastructural alterations, ER stress, and proteasome inhibition. Conclusion: External and internal porphyrinogenic stress cause compartment-selective proteotoxic damage and protein aggregation. Significance: Subcellular compartment-specific and porphyrin-selective protein aggregation may be a hallmark injury mechanism in porphyrias.