156P University of Cambridge
Summer Meeting July 2005

 

Cardiovascular effects of dendroaspis natriuretic peptide (DNP) in conscious, wistar and Sprague-Dawley rats

S M Gardiner, J E March, P A Kemp & T Bennett, School of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, UK.

DNP was originally isolated from the venom of the green mamba snake (Dendroaspis angusticeps), and is structurally and functionally similar to the other natriuretic peptides (Schweitz et al., 1992). Vaso- and veno-dilator effects of DNP have been described in vitro (Best et al., 2002), and we have now assessed the regional haemodynamic effects of DNP in vivo. Male, Charles River Wistar (n=8) and Sprague-Dawley (n=6) rats, weighing 350-450g, had pulsed Doppler flow probes and intravascular catheters (distal aorta, jugular vein) implanted under general anaesthesia (fentanyl and medetomidine, 300 µg kg-1 of each i.p.) in a two-stage surgical procedure separated by at least 10 days. Starting 24h after the last surgical stage (catheterisation), heart rate (HR), mean blood pressure (BP) and renal (R), mesenteric (M) and hindquarters (H) vascular conductances (VC) were recorded from conscious, unrestrained animals. On Day 1, after a period of baseline recording, i.v. infusions of DNP (10, 50, 100 and 500 ng kg-1 min-1 in ascending order) or saline (0.4ml h-1) were given for 45 min, separated by 60 min. Animals that were given saline on Day 1 were given DNP on Day 3 and vice versa. Some of the results are presented in Table 1.

Table 1.

Time (h) 0 0.75 1.75 2.5 3.5 4.25 5.25 6
  B10 E10 B50 E50 B100 E100 B500 E500
Wistar rats (n=8)          
HR
(b min-1) 		337±6 335±7 332±7 281±9* 289±9* 256±6* 286±11* 267±7*
BP
(mmHg) 		113±3 116±3 112±3 90±3* 96±4* 88±4* 89±2* 86±3*
RVC
(units)		 75±3 64±3* 64±3* 63±3* 67±5* 58±3* 65±3* 61±4*
MVC
(units) 		64±4 51±4* 54±5* 51±4* 51±5* 48±6* 53±4* 53±5*
HVC
(units) 		39±4 32±4* 33±4* 32±4* 25±3* 26±3* 25±2* 26±3*
Sprague Dawley rats (n=6)          
HR
(b min-1) 		347±7 351±11 345±13 332±7 339±14 312±18* 340±5 330±18
BP
(mmHg) 		116±5 118±6 116±7 100±5* 99±4* 92±4* 96±2* 92±3*
RVC
(units) 		67±5 56±4* 58±4* 56±6* 58±5* 57±5* 61±6* 60±6*
MVC
(units) 		72±10 59±9* 52±5* 45±4* 60±7 56±6* 57±6* 49±5*
HVC
(units) 		45±5 32±5* 36±5* 29±5* 28±5* 27±5* 28±5* 28±5*

In both strains, the lowest dose of DNP caused vasoconstriction with no change in BP or HR. At higher doses, there was a fall in BP accompanied by marked peripheral vasoconstriction, with little or no recovery between doses. In Wistar rats, DNP caused marked bradycardia, whereas in Sprague-Dawley rats the changes in HR were more variable and less substantial.It is likely that the hypotensive effect of DNP in conscious rats is due to a fall in cardiac output secondary to renal and/or veno-dilating actions of the peptide, offset by reflex vasoconstriction. The bradycardic effect may involve vagal afferent sensitization, as seen with other natriuretic peptides (Thomas et al., 1999), and our findings suggest the magnitude of this effect is strain-dependent.

Best, J.M. et al. (2002). Cardiovasc. Res., 55, 375-384.
Schweitz, H. et al. (1992). J. Biol. Chem., 267, 13928-13932.
Thomas, C.J. et al. (1999). J. Hypertens., 17, 801-806.