title: Hypertension's 3 Dilemmas and 3 Solutions: Pharmacology of the Kidney in Hypertension.
abstract: The Hypertension Community has 3 conflicting dilemmas: a goal systolic pressure of 120 mm Hg or less (the SPRINT Trials), 40% of our 60,000,000 hypertensives still sustain blood pressures above 140/90 mm Hg, and our most potent antihypertensive drug minoxidil sits on the sidelines, imprisoned in the Food and Drug Administration's Black Box designation. My solutions to these dilemmas are: (1) review of the facts of our most potent antihypertensive drug minoxidil which is essentially free of toxicity, (2) treatment focus on the fundamental cause of high blood pressure, that is excess dietary sodium and, (3) prevention of, and/or reversal of, the fundamental mechanism of worsening hypertension, arteriolar hypertrophy.
  
  
  CONCLUSIONS
  The Hypertension Community has 3 conflicting dilemmas: a goal systolic pressure of 120 mm Hg or less (the SPRINT Trials), 40% of our 60,000,000 hypertensives still sustain blood pressures above 140/90 mm Hg, and our most potent antihypertensive drug minoxidil sits on the sidelines, imprisoned in the Food and Drug Administration's Black Box designation. My solutions to these dilemmas are: (1) review of the facts of our most potent antihypertensive drug minoxidil which is essentially free of toxicity, (2) treatment focus on the fundamental cause of high blood pressure (HBP) and excess dietary sodium and, (3) prevention of, and/or reversal of, the fundamental mechanism of worsening hypertension, arteriolar hypertrophy. My focus at UT Southwestern in Dallas was on extremely severely hypertensive patients with a quantifiable, measurable complication of HBP, progression of nephrosclerotic damage to kidneys. This model had the greatest likelihood of exposing fundamental disregulatory mechanisms in hypertensive patients (which it did) and the potential for study of the most relevant antihypertensive drug interactions to achieve optimal blood pressure control (which it did). By maintaining diastolic pressures at 80 mm Hg or less in the first National Institutes of Health-supported, long-term randomized clinical trial to save the kidneys, the bases for a fundamental blood pressure support mechanism (arteriolar hypertrophy) was illuminated but not fully described until now. This fundamental hypertensinogenic mechanism results from HBP but with time and severity, becomes its own raison d'être. I am now aged 84 years. As a result of a stroke 20 years ago, which caused permanent double vision, and because of poor blood pressure control with triple therapy, I started using minoxidil 5 mg/d along with atenolol and occasional furosemide. Now, along with some dietary salt restriction, my resting blood pressure is 110/65-125/75 and, despite >30 years history of HBP, I have no retinal arteriolar hypertrophy nor arcus senilis (Dr. Schwartz-U. of Miami) which is almost universally present at this age. Yes, prevention of, or reversal of, arteriolar hypertrophy should be a central focus of HBP treatment. I simply wish to share a bit of accumulated wisdom that might be of use to others.
authors.affiliation: Division of Clinical Pharmacology (Retired), University of Texas Southwestern Medical School (Retired), Bonita Springs, FL.
authors.forename: William A
authors.initials: WA
authors.lastname: Pettinger
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008914:Minoxidil / Q000494:pharmacology / Q000627:therapeutic use*; D017673:Sodium Chloride, Dietary / Q000009:adverse effects
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D017673:Sodium Chloride, Dietary; D008914:Minoxidil