Is the Widening of Pulse Pressure and Hypertension in the Elderly Due in Large Measure to an Unrecognized Hypomagnesemia, Downregulation of Telomerase and Progressive Release of Ceramides and Platelet-Activating Factor?

the Widening of Pulse and Hypertension in the Due in Large Measure to an Unrecognized Hypomagnesemia, Downregulation of Telomerase and Progressive Release of Ceramides and Platelet-Activating Factor?. Biomed Abstract


Commentary
It is generally agreed that age-related increases in arterial blood pressure (ABP) are mainly a reflection of an increase in systolic blood pressure (SBP) while maintaining or exhibiting a slight decrease in a diastolic blood pressure (DBP). This situation results in a widening of pulse pressure (PP) (i.e., the difference between SBP and DBP). It is generally thought that a widening of PP can be due to several different factors:
Whatever the exact cause, this often leads to atrial fibrillation (AF) and is associated with coronary arterial disease or a heart attack. Often a change in diet and lifestyle changes can ameliorate the condition. If not, various medications are given to the patient such as angiotensin II converting enzyme inhibitors, beta-blockers, folic acid plus pyridoxine, and a variety of antihypertensive drugs.

Decreased Dietary Intake of Mg Found in North American and European Populations and Risks for Cardiovascular Diseases and Strokes
At the turn of the last century, the North American and It has been shown, in multiple studies, that people drinking softwater (e.g., <10 mg/l of Mg) demonstrate a high risk for coronary arterial diseases, ischemic heart disease, hypertension, and strokes, whereas those peoples drinking hard-waters have low risks for these cardiovascular diseases and strokes [20,21].

Evidence for Progressive Release of Ceramides and Platelet-Activating Factor with Widening of Pulse Pressure in Experimental Mg Deficiency
About 25 years ago, working with isolated cerebral vascular and aortic smooth muscle cells, and 1H-nuclear magnetic resonance spectroscopy, our group found that decreased extracellular Mg resulted in an increase in sphingolipids, particularly ceramides, increases in platelet-activating factor (PAF) and PAF-like lipids [22,23]. All three of these classes of molecules can cause constriction/contraction of microvascular arterioles and venules as well as cerebral and coronary blood vessels [24][25][26].  [26][27][28][29][30]. A few years later, we noticed that when primary cultured vascular smooth muscle cells (i.e., piglet coronary, cerebral vascular and aortic smooth muscle cells) were exposed to media with low Mg 2+ , there was a rapid rise in cellular PAF levels which could be inhibited with specific PAF receptor blockers; the longer the primary cells were kept in low [Mg 2+ ]0 , up to a point, the greater the release of PAF-like lipids [31].
In view of such new experiments, we went-on to determine if the rises in PP in Mg-deficient animals were correlated positively with incremental rises in ceramides and PAF. We were not surprised that the answer was "yes" and that these rises in ceramides, PAF and PP could be significantly ameliorated with inhibitors of ceramide and PAF synthesis (P<0.01) [31].

Progressive Decrease of Ionized Magnesium Results in a Progressive Downregulation of Telomerase
Working with rats fed low Mg diets for 21 days, we found that cardiovascular tissues and cells demonstrated a downregulation of telomerases and oxidation of DNA [32]. Using specific ELISA assays, we found that the extirpated cardiovascular tissues and cells showed that, as the ionized Mg fell in both the blood and cardiovascular tissues, there was a greater and greater downregulation of telomerases and oxidation of DNA [31]. As we have previously suggested [32], these studies would be compatible with the idea that even short-term Mg deficiency in the aging process could cause alterations in the genome that would result in atherogenesis and increases in PP in the elderly.