A recent novel observation was the occurrence of a biphasic tachycardic and hindquarters vasodilator response to bolus injection of hUII in conscious rats. An early phase, 5-10 min post-injection, was followed by recovery and then a second phase, 90-120 min post-injection (Gardiner et al., 2003). We have now investigated the possible involvement of nitric oxide (NO) in the effects observed.

Under anaesthesia (fentanyl and medetomidine, 300 µg kg^-1 of each i.p. reversed with nalbuphine and atipamezole, 1 mg kg^-1 of each s.c.), 9 male, Sprague-Dawley rats (400-450g) had pulsed Doppler flow probes and, at least 14 days later, intravascular catheters, implanted. On the day following catheterisation, measurements of mean arterial blood pressure (BP), heart rate (HR) and renal (R), mesenteric (M) and hindquarters (H) vascular conductances (VC) were made. Rats were given hUII (3 nmol kg^-1 i.v.) 90 min after the onset of saline (0.1ml bolus, 0.4 ml h^-1 infusion) on Day 1, or of L-NAME (3 mg kg^-1, 3 mg kg^-1
h^-1) on Day 2. Some of the results are shown in Table 1.

		Before	5min		90min
			Absolute %		Absolute %
HR	S	344±12	+63±11	+18±4*	+49±13	+15±4*
	L	293±13†	+100±12	+35±5*†	+5±15†	+2±5†
BP	S	109±4	-7±2	-7±2*	+9±2	+8±2*
	L	134±5†	-8±5	-5±3*	+8±4	+6±3
MVC	S	100±9	+29±5	+32±7*	-8±2	-8±2*
	L	51±5†	+19±5 *	+40±10	-4±3	-7±6
HVC	S	35±5	+10±2	+31±5*	+11±2	+34±3*
	L	18±2†	+9±2	+53±8*†	-4±2†	-17±9†

Table 1. HR (beats min^-1), BP (mmHg), MVC and HVC ([kHz mmHg^-1]10³) before, and changes () after hUII in rats (n=9) infused with saline (S) or L-NAME (L). Values are mean ±s.e.mean. * P<0.05 vs before UII (Friedman's) † P<0.05 vs saline (Wilcoxon's)

In the presence of saline, the haemodynamic effects of hUII were as described before, i.e., short-lived mesenteric vasodilatation, biphasic tachycardia and hindquarters vasodilatation, with modest changes in BP, and no change in RVC (not shown). Administration of L-NAME caused an increase in BP, fall in HR, and widespread vasoconstriction. In the presence of L-NAME, the initial hindquarters vasodilator and tachycardic responses to hUII were not changed (absolute ) or greater (%) than those seen in the presence of saline, whereas the later increases in HVC and HR were abolished. The hUII-induced increase in MVC was unaffected by L-NAME, despite the underlying vasoconstriction caused by the latter. The results are consistent with an involvement of NO in the late-onset cardiovascular effects of hUII in conscious rats. The source of the NO remains to be determined.

Gardiner, S.M. et al. (2003). Br. J. Pharmacol., suppl (in press).

This work was supported by the British Heart Foundation.