Introduction:

Endothelin-1 (ET-1) is involved in several models of hypertension. ET-1 stimulates sensory motor nerves to release calcitonin gene-related peptide (CGRP) which plays a counterbalancing role in salt sensitive hypertension. We tested the hypothesis that ET-1 and CGRP interact during the development of other forms of experimental hypertension.

Methods:

ET-1 and CGRP contents were measured by radioimmunoassay in heart, kidney and lung of young SHR (6, 8 and 12 weeks), and WKY. The same measurements were performed after a 4 week activation of renin in 8 and 34 weeks old inducible renin-dependent Cyp1A1 Ren2 transgenic rat (CR). The correlations between ET-1 and CGRP include data of all 3 organs.

Results:

In 6 weeks old WKY and SHR ET-1 and CGRP levels were similar (ET-1 WKY: 5.2±0.6; SHR: 4.4±0.5 fmol/mg protein; CGRP WKY: 4.5±0.4; SHR 4.0±0.5 fmol/mg protein). At 8 weeks of age both ET-1 and CGRP levels were significantly increased (ET-1: 20.4±6.3 fmol/mg protein, p=0.0367; CGRP: 9.1±0.9 fmol/mg protein, p=0.0003). Moreover ET-1 and CGRP levels were positively correlated (p=0.0026, r² =0.75). At 12 weeks the correlation failed to reach significance mainly because in the lung elevated ET-1 levels were not accompanied by a similar increase in CGRP levels. A positive correlation between ET-1 and CGRP content was also found in 8 week old controls and induced CR rats (p=0.0023, r² =0.75 and p=0.0003, r² =0.87) respectively. At 34 weeks a positive correlation was found in the controls only (p=0.0154, r² =0.59). In the induced group correlations failed to reach significance for reasons described in the 12 weeks SHR.

Conclusion:

During hypertension tissue levels of ET- 1 and CGRP are correlated. In contrast, a correlation could not be observed in established hypertension (12 week old SHR and 34 week old CR rat). The increased pulmonary ET-1 levels could result from clearance.

This study was performed within project T2-108 of the Dutch TIPharma.