Effect of a nonhypotensive long-term infusion of ANP on the mechanical and structural properties of the arterial wall in Wistar-Kyoto and spontaneously hypertensive rats.

Abstract

A nonhypotensive dose of atrial natriuretic peptide (ANP) was infused (60 pg/kg body wt per day s.c. by osmotic pump) for 25 days in 16-week-old normotensive Wistar-Kyoto rats (WKYs, TI = 12) and age-matched spontaneously hypertensive rats (SHRs, n = 12). During the infusion period, systolic blood pressure, urinary volume, and cyclic guanosine monophosphate (cGMP) excretion/12 hr were measured once a week in both groups. Then mechanical and morphological properties of the arterial wall and plasma ANP levels were assessed and compared with those from control groups of SHRs («=8) and WKYs (n=8) receiving a saline vehicle. The compliance (CC) of the in situ localized carotid artery was measured for pressures ranging from 25 to 175 mm Hg under control conditions and after "poisoning" of smooth muscle tone by potassium cyanide. After pressure fixation, the medial thickness, elastin and collagen contents, and the size and number of nuclei were measured in the thoracic descending aorta. In WKYs, ANP did not modify either mechanical or structural properties of the arterial wall or biochemical parameters. Conversely, in ANP-treated SHRs, CC was significantly increased compared with untreated SHRs under basal conditions (p<0.03) and after potassium cyanide poisoning (/><0.02). Structural properties were also modified by ANP in SHRs, i.e., medial thickness (129.3±4.1 versus 113.1 ±3.3 jum, p<0.01) and nuclear size (8.81 ±0.28 versus 5.52±0.20 /i.m\p<0.0001) in untreated and treated SHRs, respectively. Furthermore, urinary volume and cGMP content were significantly increased during ANP infusion in treated SHRs (p<0.05). The present results indicate concomitant modifications of mechanical and structural properties of the arterial wall in SHRs chronically treated with low doses of ANP. These long-term effects of ANP could be involved in the remodeling of the arterial wall observed during hypertension and could have beneficial effects on cardiovascular diseases in chronic sustained hyperten- fects such as an increase of diuresis, natriuresis, J. JL urinary excretion of cyclic guanosine monophosphate (cGMP), and glomerular filtration rate and a selective regional relaxation of vascular smooth muscle cells 1 that is partially mediated by the activation of particulate guanylate cyclase via its second messenger, cGMP. The vasorelaxant effects of ANP have been extensively demonstrated in in vitro preparations 2 -4 but not so much in in vivo models. Recent studies have demonstrated that long-term infusion of ANP at low doses reduces blood pressure in several animal models of hypertension, including spontaneously hypertensive rats (SHRs). 5 -8 In this strain, it has been previously shown that the antihypertensive properties were more Received August 13, 1992; revision accepted October 30, 1992. marked when the plasma levels of ANP were modestly but chronically elevated than when they were markedly and acutely increased. 8In SHRs, elevated systemic resistances are associated with an increase in arteriolar and arterial wall thickne...

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