The Effect of Acetyl Salicylic Acid Induced Nitric Oxide Synthesis in the Normalization of Hypertension through the Stimulation of Renal Cortexin Synthesis and by the Inhibition of Dermcidin Isoform 2, A Hypertensive Protein Production.

Currently, there is no specific medication for essential hypertension (EH), a major form of the condition, in man. As acetyl salicylic acid (aspirin) is reported to stimulate the synthesis of renal (r)-cortexin, an anti-essential hypertensive protein, and, as aspirin is reported to inhibit dermcidin isoform 2 (dermcidin), a causative protein for EH, the role of aspirin in the control of EH in man was studied. Oral administration of 150 mg aspirin/70 kg body weight in subjects with EH was found to reduce both the elevated systolic and diastolic blood pressures to normal levels within 3 h due to the normalization of dermcidin level in these subjects. The plasma cortexin level at day 0, 1, 30 and 90 were 0.5 pmol/ml, 155.5 pmol/ml, 160.2 pmol/ml, 190.5 pmol/ml respectively with increased NO synthesis (r=+0.994). In vitro studies demonstrated that the incubation of the goat kidney cortex cells with aspirin stimulated (r)-cortexin synthesis due to NO synthesis. It could be suggested that the use of aspirin might control EH in man.

Diagnosis of essential hypertension in humans by the determination of plasma renal cortexin using enzyme-linked immunosorbent assay.

BACKGROUND: More than 90% of all hypertensive persons are reported to have essential hypertension (EH), a particular form of elevated blood pressure, for which no diagnostic test is currently available. The level of plasma renal (R) cortexin (PRC), a hypotensive protein produced in the kidney cortex cells, was reported to be reduced from 218 nM in the plasma of normotensive persons (NP) to 0 nM in the plasma of patients with EH. The feasibility of using the determination of PRC by enzyme-linked immunosorbent assay (ELISA) as a diagnostic test for EH was investigated. METHODS: The PRC was determined by ELISA using electrophoretically pure cortexin as the antigen. A total of 344 persons (male and female) with EH, with or without diabetes mellitus (DM), and receiving or not receiving any anti-hypertensive and/or anti-diabetic medication at presentation, as well as an equal number of age- and gender-matched NP participated in the study. RESULTS: All persons with EH, with or without co-existing DM, were found to have 0 nM PRC, regardless of whether they were receiving anti-hypertensive and anti-diabetic drugs, including those who had been taking these medications over an extended period of time (3 months). CONCLUSIONS: The determination of PRC as a marker protein by ELISA, a rapid method that can be carried out in any diagnostic laboratory, was shown to be suitable for the diagnosis of EH, even in those subjects who had co-existing DM and were receiving both anti-hypertensive and anti-diabetic medication.

The role of dermcidin isoform 2: a two-faceted atherosclerotic risk factor for coronary artery disease and the effect of acetyl salicylic Acid on it.

Hypertension and diabetes mellitus are considered to be two major atherosclerotic risk factors for coronary artery disease (CAD). A stress-induced protein identified to be dermcidin isoform 2 of Mr. 11 kDa from blood plasma of hypertensive persons when injected (0.1 µM) in rabbits increased the systolic pressure by 77% and diastolic pressure by 45% over the controls within 2 h. Ingestion of acetyl salicylic acid (150 mg/70 kg) by these subjects reduced systolic (130 mm Hg) and diastolic pressures (80 mm Hg) with reduction of plasma dermcidin level to normal ranges (9 nM). The protein was found to be a potent activator of platelet cyclooxygenase and inhibited insulin synthesis. Aspirin was found to reduce hypertension by reduction of plasma dermcidin level, neutralized the effect of cyclooxygenase, and restored the pancreatic insulin synthesis through NO synthesis. These results indicated that dermcidin could be a novel atherosclerotic risk factor for its hypertensive and diabetogenic effects.