Purification and mechanism of action of "cortexin," a novel antihypertensive protein hormone from kidney and its role in essential hypertension in men.
Because kidney tissue damage is associated with both hypertension and impaired nitric oxide (NO) production, we investigated the possibility whether the kidney tissue contains any activator of endothelial NO synthase (eNOS) that could be important in essential hypertension. An activator protein of M(r) 43000 Da for eNOS from the goat kidney cortex homogenate was purified to homogeneity by chromatographic techniques. This activator trivially, called "cortexin," was determined by enzyme-linked immunosorbent assay using anticortexin antibody. NO was determined by the formation of methemoglobin. Injection of 0.5 nmol cortexin/kg body weight to rabbit pretreated with l-epinephrine that increased the systolic and diastolic pressures to 195 +/- 3.40 mm Hg and 98.14 +/- 6.64 mm Hg, respectively, reduced and kept the elevated pressures at normal ranges of 133.57 +/- 12.14 (systolic) and 51.03 +/- 3.21 (diastolic) for 45 hours with simultaneous increase of plasma NO level. The inhibition of cortexin-induced NO synthesis nullified the antihypertensive effect of cortexin. The plasma cortexin level in newly diagnosed persons with essential hypertension was 0 pmol/mL (median), which contrasted with 218.94 pmol cortexin/mL (median), in normotensive persons (P < .0005; n = 25). We concluded that the impaired production of cortexin in the cortex of kidney might lead to essential hypertension.
Chakraborty
Somashree
S
Sinha Institute of Medical Science & Technology, Garia, Calcutta, India.
Khan
Gausal A
GA
Karmohapatra
Soumendra K
SK
Bhattacharya
Rabindra
R
Bhattacharya
Gorachand
G
Sinha
A Kumar
AK