Regional heterogeneity in the haemodynamic responses to urotensin II infusion in relation to UT receptor localisation

Abstract

The aim of the study was to measure regional haemodynamic responses to 6 h infusions of human urotensin II (hUII), to identify possible mediators of the effects observed, and to relate the findings to the distribution of urotensin II receptors (UT receptors). Male, Sprague-Dawley rats had pulsed Doppler flow probes and intravascular catheters implanted for measurement of regional haemodynamics in the conscious, freely moving state. Infusions of saline (0.4 ml h(-1)) or hUII (30, 300 and 3,000 pmol kg(-1) h(-1)) were given i.v. for 6 h, and the effects of pretreatment with indomethacin (5 mg kg(-1) h(-1)), N(G)-nitro-L-arginine methyl ester (L-NAME, 3 mg kg(-1) h(-1)) or propranolol (1 mg kg(-1); 0.5 mg kg(-1) h(-1)) on responses to hUII (300 pmol kg(-1) h(-1) for 6 h) were assessed. Cellular localisation of UT receptor-like immunoreactivity was determined in relevant tissues. hUII caused dose-dependent tachycardia and hindquarters vasodilatation, accompanied by a slowly developing rise in blood pressure. Haemodynamic effects of hUII were attenuated by propranolol or L-NAME and abolished by indomethacin. UT receptor-like immunoreactivity was detected in skeletal and vascular smooth muscle. The findings indicate that in conscious rats, infusions of hUII cause vasodilatation, which, of the vascular beds monitored, is selective for the hindquarters and dependent on cyclooxygenase products and nitric oxide. The pressor effect of hUII under these conditions is likely to be due to an increase in cardiac output, possibly due to a positive inotropic effect. UT receptor-like immunoreactivity present in skeletal muscle is consistent with the haemodynamic pattern.

Figure 1

Haemodynamic responses to i.v. infusions of saline (dotted line, n=8) or human UII at 30 (filled circles, n=9), 300 (open circles, n=9) and 3000 (filled squares, n=8) pmol kg⁻¹ h⁻¹ for 6 h in conscious rats. Values are mean and vertical bars represent s.e.m. For clarity, data points have been omitted from the saline group, and error bars omitted from the saline and 30 pmol kg⁻¹ h⁻¹ groups. ^*P<0.05 vs baseline (Friedman's test).

Figure 2

Haemodynamic responses to i.v. infusion of human UII (300 pmol kg⁻¹ h⁻¹) in the presence of indomethacin (5 mg kg⁻¹ h⁻¹, open circles) or its vehicle (10 nM Na₂CO₃ at 0.4 ml h⁻¹, filled circles) in conscious rats (n=8). Values are mean and vertical bars represent s.e.m. ^*P<0.05 vs baseline (Friedman's test).

Figure 3

Haemodynamic responses to i.v. infusion of human UII (300 pmol kg⁻¹ h⁻¹) in the presence of L-NAME (3 mg kg⁻¹ h⁻¹, open circles) or its vehicle (saline at 0.4 ml h⁻¹, filled circles) in conscious rats (n=8). Values are mean and vertical bars represent s.e.m. ^*P<0.05 vs baseline (Friedman's test).

Figure 4

Haemodynamic responses to i.v. infusion of human UII (300 pmol kg⁻¹ h⁻¹) in the presence of propranolol (1 mg kg⁻¹, 0.5 mg kg⁻¹ h⁻¹, open circles; n=6) or its vehicle (saline, 0.1 ml, 0.4 ml h⁻¹, filled circles; n=4) in conscious rats. Values are mean and vertical bars represent s.e.m. ^*P<0.05 vs baseline (Friedman's test).

Figure 5

Light photomicrographs showing localisation of UT receptor-like immunoreactivity to (a) a transverse section through rat skeletal muscle (skm) and to the smooth muscle (sm) layer of an associated artery (a) and vein (v). (b) Negative control in which the UT receptor antiserum was omitted in an adjacent section of skeletal muscle. Scale bar=200 μm.