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J Robert Cade

Publications and source records attributed to J Robert Cade.

2 recordsLinked to original sources

Uric acid, evolution and primitive cultures.

Hypertension is epidemic and currently affects 25% of the world's population and is a major cause of stroke, congestive heart failure, and end-stage renal disease. Interestingly, there is evidence that the increased frequency of hypertension is a recent event in human history and correlates with dietary changes associated with Westernization. In this article, we review the evidence that links uric acid to the cause and epidemiology of hypertension. Specifically, we review the evidence that the mutation of uricase that occurred in the Miocene that resulted in a higher serum uric acid in humans compared with most other mammals may have occurred as a means to increase blood pressure in early hominoids in response to a low-sodium and low-purine diet. We then review the evidence that the epidemic of hypertension that evolved with Westernization was associated with an increase in the intake of red meat with a marked increase in serum uric acid levels. Indeed, gout and hyperuricemia should be considered a part of the obesity, type 2 diabetes, and hypertension epidemic that is occurring worldwide. Although other mechanisms certainly contribute to the pathogenesis of hypertension, the possibility that serum uric acid level may have a major role is suggested by these studies.

Animals↗

Genetic AT1A receptor deficiency attenuates cold-induced hypertension.

The aim of this study was to test our hypotheses that AT1A receptors play a role in the pathogenesis of cold-induced hypertension (CIH) and in the cold-induced increase in drinking responses to ANG II. Two groups of wild-type (WT) and two groups of AT1A receptor gene knockout (AT1A-KO) mice were used (6/group). Blood pressures (BP) of the four groups were similar during the control period at room temperature (25 degrees C). After the control period, one group of WT and one group of AT1A-KO mice were exposed to cold (5 degrees C), while the remaining groups were kept at 25 degrees C. BP of the cold-exposed WT group elevated significantly within 1 wk of exposure to cold and increased gradually to a maximum level by week 5. However, there was only a slight increase in BP of the cold-exposed AT1A-KO group. The maximal cold-induced increase in BP (DeltaBP) is significantly less in AT1A-KO group (11 +/- 3 mmHg) than in WT group (49 +/- 6 mmHg), indicating that AT1A receptor deficiency attenuates cold-induced elevation of BP. Interestingly, both WT and AT1A-KO mice developed cardiac and renal hypertrophy to the same extent. AT1A-KO caused a significant increase in urine and plasma levels of nitric oxide (NO), indicating that the renin-angiotensin system inhibits NO formation probably via AT1A receptors. Cold exposure inhibited endothelial NO synthase protein expressions and decreased urine and plasma levels of NO, which may be mediated partially by AT1A receptors. AT1A-KO completely abolished the cold-induced increase in drinking responses to ANG II. We conclude that 1) AT1A receptors play an essential role in the pathogenesis of CIH but not cardiac hypertrophy; 2) the role of AT1A receptors in CIH may be mediated partially by its inhibitory effect on the NO system; and 3) cold-induced increase in drinking response to ANG II is mediated by AT1A receptors.

Angiotensin II↗