Is Maternal Blood Pressure the Key to Vascular Dysfunction in Preterm Offspring With Elevated Blood Pressure?

Background: Psoriasis is hallmarked by vascular dysfunction, arterial hypertension, and an increased risk for cardiovascular diseases. We have shown recently that skin-driven interleukin (IL)-17A expression promotes psoriasis-like disease in mice, and this is associated with vascular inflammation, vascular dysfunction, and hypertension. As an intensive risk-factor reduction is recommended for psoriasis patients, we aimed to elucidate the impact of the angiotensin II receptor type 1 (AT1) antagonist telmisartan in a mouse model of severe psoriasis-like skin disease. Methods and Results: Elevated blood pressure measured by tail-cuff plethysmography in mice with keratinocyte-specific IL-17A overexpression (K14-IL-17Aind/+ mice) was significantly reduced in response to telmisartan. Importantly, vascular dysfunction, as assessed by isometric tension studies of isolated aortic rings, vascular inflammation measured by flow cytometry analysis of CD45+CD11b+ immune cells, as well as the increased peripheral oxidative stress levels assessed by L-012-enhanced chemiluminescence were not attenuated by telmisartan treatment of K14-IL-17Aind/+ mice, nor was the persisting skin inflammation. Conclusion: We provide first evidence for an effective antihypertensive treatment in experimental psoriasis by AT1 blockade, but without any impact on vascular inflammation and dysfunction in our mouse model of severe psoriasis-like skin disease. This suggests that vascular function and inflammation in psoriasis might not be attenuated as long as skin inflammation persists.

Download Full-text

Mechanisms underlying developmental programming of elevated blood pressure and vascular dysfunction: evidence from human studies and experimental animal models

Clinical Science ◽

10.1042/cs20070113 ◽

2007 ◽

Vol 114 (1) ◽

pp. 1-17 ◽

Cited By ~ 119

Author(s):

Anne Monique Nuyt

Keyword(s):

Blood Pressure ◽

Vascular Dysfunction ◽

Renin Angiotensin System ◽

Later Life ◽

Epidemiological Studies ◽

Experimental Models ◽

Elevated Blood Pressure ◽

Elevated Blood ◽

Early Life Conditions

Cardiovascular-related diseases are the leading cause of death in the world in both men and women. In addition to the environmental and genetic factors, early life conditions are now also considered important contributing elements to these pathologies. The concept of ‘fetal’ or ‘developmental’ origins of adult diseases has received increased recognition over the last decade, yet the mechanism by which altered perinatal environment can lead to dysfunction mostly apparent in the adult are incompletely understood. This review will focus on the mechanisms and pathways that epidemiological studies and experimental models have revealed underlying the adult cardiovascular phenotype dictated by the perinatal experience, as well as the probable key causal or triggering elements. Programmed elevated blood pressure in the adult human or animal is characterized by vascular dysfunction and microvascular rarefaction. Developmental mechanisms that have been more extensively studied include glucocorticoid exposure, the role of the kidneys and the renin–angiotensin system. Other pathophysiological pathways have been explored, such as the role of the brain and the sympathetic nervous system, oxidative stress and epigenetic changes. As with many complex diseases, a unifying hypothesis linking the perinatal environment to elevated blood pressure and vascular dysfunction in later life cannot be presumed, and a better understanding of those mechanisms is critical before clinical trials of preventive or ‘deprogramming’ measures can be designed.

Download Full-text

Hypertension Predicted by Tracking of Elevated Blood Pressure From Childhood to Adulthood

Journal of the American College of Cardiology ◽

10.1016/s0735-1097(97)88093-x ◽

1998 ◽

Vol 31 (2) ◽

pp. 481A

Author(s):

M Macedo

Keyword(s):

Blood Pressure ◽

Elevated Blood Pressure ◽

Elevated Blood

Download Full-text

ROLE OF THE THYROID GLAND IN DEVELOPMENT AND MAINTENANCE OF RENAL HYPERTENSION IN RATS

Acta Endocrinologica ◽

10.1530/acta.0.xxxiv0411 ◽

1960 ◽

Vol XXXIV (III) ◽

pp. 411-429 ◽

Cited By ~ 3

Author(s):

Melvin J. Fregly ◽

Kenneth M. Cook

Keyword(s):

Blood Pressure ◽

Rate Increase ◽

Renal Hypertension ◽

The Other ◽

Elevated Blood Pressure ◽

Unit Weight ◽

Elevated Blood ◽

Inhibition Of Growth ◽

Testicular Size

ABSTRACT The anti-thyroid drugs, thiouracil, propylthiouracil, and methimazole, prevented both development of elevated blood pressure and cardiac hypertrophy usually accompanying kidney encapsulation with latex envelopes. These drugs also reduced elevated blood pressure of rats with hypertension of 13 to 40 weeks' duration prior to drug administration. Addition of desiccated thyroid powder to diet containing an anti-thyroid drug overcame the anti-hypertensive effect of the latter. Withdrawal of thyroid powder only was followed by return of blood pressure to previous low level within 3 weeks. The results suggest that the anti-hypertensive effect of these drugs is related directly to the hypothyroidism produced rather than to extrathyroidal effects of the drugs. Comparison of potencies of the 3 drugs in terms of anti-hypertensive effect, inhibition of growth rate, increase in testicular size, and increase in thyroid size suggests that propylthiouracil and methimazole are equally potent per unit weight of drug. Thiouracil has approximately half the potency of the other two.

Download Full-text