Evaluation of calcitonin gene- related peptide in hypertension: a clinical and experimental study

ABSTRACT

Calcitonin gene-related peptide [CGRP] is an extremely potent vasodilator neuropeptide that is widely distributed in the perivascular sensory nerves. To clarify the exact role of CGRP in hypertension in both essential hypertension patients and experimentally induced hypertension in rats. 15 patients with untreated essential hypertension and 15 age and sex matched healthy controls were subjected to physical examination, resting ECG, two-dimensional echocardiography, abdominal ultrasound, Doppler study of renal vessels, and laboratory tests including estimation of serum CGRP, malondialdehyde [MDA; as an oxidative stress marker], renal functional parameters and other essential investigations. In the experimental study, hypertension was induced in 15 male albino rats by uninephrectomy and 0.9% saline in drinking water for 6 weeks [uninephrectomy-salt model]. 15 matched healthy male albino rats [controls] were sham operated and given tap water. Rats were subjected to mean arterial pressure [MAP] measurement, using a pressure transducer, and laboratory tests including serum CGRP, MDA and renal function tests. Compared with normotensive controls, essential hypertension patients had a significantly higher mean serum creatinine [P= 0.011], urinary albumin excretion [UAE], and serum MDA versus a significantly reduced CGRP [P<0.001]. Echocardiography revealed subtle hypertensive findings in only 3 patients. All ECGs were normal. Hypertensive rats showed a significantly higher mean blood urea, serum creatinine, UAE, serum MDA, and also CGRP than control rats [P<0.001]. In hypertensive patients, the only observed correlation was a positive correlation between the systolic blood pressure and serum MDA [r =0.52, P =0.037]. In hypertensive rats, a positive correlation was observed between each of MAP, UAE and serum MDA [r =0.65, P =0.008 and r =0.62, P = 0.012] and also between MAP and serum CGRP [r =0.59, P =0.017], versus an inverse correlation between UAE and CGRP [r = -0.54, P =0.026]. In addition, a strongly positive correlation was observed between serum MDA and CGRP in the hypertensive rats [r =0.77, P<0.001]. Patients with essential hypertension have diminished CGRP levels. Hypertension is associated with increased oxidative stress. CGRP is important in protection against hypertension-induced renal damage. These data shed light on a potentially therapeutic role of CGRP and may be antioxidants in the management of hypertension, including the use of medications that can enhance CGRP release, or increase the vascular sensitivity to this neuropeptide