-Adrenoceptors: Challenges and Opportunities-Enlightenment from the Kidney.

It was indeed a Don Quixote-like pursuit of the mechanism of essential hypertension when we serendipitously discovered -adrenoceptors ( -ARs) in skin-lightening experiments in the frog. Now -ARs lurk on the horizon involving hypertension causality, renal denervation for hypertension, injury from falling in the elderly and prazosin's mechanism of action in anxiety states such as posttraumatic stress disorder (PTSD). Our goal here is to focus on this horizon and bring into clear view the role of -AR-mediated mechanisms in these seemingly unrelated conditions.

Hypertension's 3 Dilemmas and 3 Solutions: Pharmacology of the Kidney in Hypertension.

Unlabelled: 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.

Summary: 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.

Autonomic ganglionitis with severe hypertension, migraine, and episodic but fatal hypotension.

We report the clinical, pathologic, and immunohistochemical features of a severe hypertensive patient with recurrent migraine-induced hypotension. The patient died of migraine-induced vasomotor paralysis despite prompt institutions of fluid and sympathomimetic and parasympatholytic agents. Postmortem study revealed autonomic ganglionitis and neuritis.

Sexual dimorphism of renal alpha2-adrenergic receptor regulation in Dahl rats.

Male Dahl salt-sensitive hypertensive (S) rats develop hypertension faster than females. We measured renal alpha2-adrenergic receptor density of inbred Dahl salt-sensitive (SS/JR) and salt-resistant (SR/JR) rats, using [3H]-rauwolscine saturation binding studies. Male and female SS/JR rats were gonadectomized or sham-operated at 6 weeks of age and fed a high salt diet for 4 weeks.

"Strict" blood pressure control and progression of renal disease in hypertensive nephrosclerosis.

Hypertensive nephrosclerosis is a progressive renal disease and the leading cause of end-stage renal disease (ESRD) in blacks in the United States. It is generally believed that hypertensive renal injury is responsible for progressive renal failure; however, it is not known whether pharmacologic lowering of blood pressure to any level prevents progression of renal disease. Accordingly, we performed a long-term prospective randomized trial to determine whether "strict" [diastolic blood pressure (DBP) 65 to 80 mm Hg] versus "conventional" (DBP 85 to 95 mm Hg) blood pressure control is associated with a slower rate of decline in glomerular filtration rate.