Goldblatt hypertension is reduced by transgenic overexpression of neuropeptide Y in the rat

Neuropeptide Y (NPY) is expressed in the sympathetic nervous system and the peptide has been implicated in the central regulation of blood pressure (BP). The hypertension in the Goldblatt one‐kidney one‐clip (1K1C) model is predominantly due to sodium and fluid retentions and enhanced sympathetic nervous activity. This experiment was designed to determine if NPY is involved in the development of 1K1C hypertension in the rat. Sprague Dawley transgenic male rats (NTG) overexpressing NPY under its natural promoter and non‐transgenic littermates (CTR) were used. BP was measured by telemetry. After baseline (3 days) BP recording, the rats were subjected to 1K1C or sham surgery and telemetric recordings of BP and HR were continued for 3 weeks. Baseline BP was lower in the NTG group (by 6.5 mmHg, p<0.05). 1K1C (but not sham treatment) increased BP gradually in both groups; however the BP of the transgenic rats was significantly lower than that of the control (113.8 ±0.8 vs 135.7 ±0.2 mmHg, NTG vs CTR, respectively). During the treatment HR was not changed in the CTR but it was reduced in the NTG subjects (by 16 bpm, p<0.05). Thus, increased NPY signaling reduced the development of 1K1C hypertension. The mechanism of the hypotensive effect of NPY upregulation may involve central inhibition of the sympathetic outflow, an increase in sodium excretion, or increase of the baroreflex responsiveness. These results indicate that NPY is an antihypertensive neurotransmitter of the autonomic nervous system and that genetic deficiencies in NPY signaling may underlie the etiology of some forms of hypertension. Support: HL 57921.