Snakes and Hypertension

Inhibition of Angiotensin Conversion in Experimental Renovascular Hypertension. By Miller ED Jr, Samuels A, Haber E, and Barger AC. Science 1972; 177:1108–9. Reprinted with permission from AAAS. Constriction of the renal artery and controlled reduction of renal perfusion pressure is followed by a prompt increase in systemic renin activity and a concomitant rise in blood pressure in trained, unanesthetized dogs. The elevated blood pressure induced by the renal artery stenosis can be prevented by prior treatment with the nonapeptide Pyr-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro, which blocks conversion of angiotensin I to angiotensin II. Further, the nonapeptide can restore systemic pressure to normal in the early phase of renovascular hypertension. These results offer strong evidence that the renin– angiotensin system is responsible for the initiation of hypertension in the unilaterally nephrectomized dog with renal artery constriction.

Atrial natriuretic factor in dogs with one-kidney, one-clip Goldblatt hypertension

The temporal changes in the plasma concentration of immunoreactive atrial natriuretic factor (ANF) were studied in dogs (n = 5) before and after renal artery constriction to produce one-kidney, one-clip renovascular hypertension. Three days after renal artery constriction, circulating ANF increased from 34 +/- 7 to 344 +/- 129 pg/ml (P less than 0.05) in association with a 38-mmHg elevation of mean arterial pressure and increases in plasma renin and aldosterone levels. Plasma renin and aldosterone remained elevated for 9 days after renal artery constriction. Arterial pressure stabilized at this elevated level of 35-40 mmHg above base line for the duration of the 4 wk after renal artery constriction. Right atrial filling pressure did not change significantly (P greater than 0.05) after constriction of the renal artery. This observation suggests that volume expansion with right atrial distention is not the only stimulus for release of ANF in these hypertensive dogs. Plasma ANF remained significantly elevated above base-line levels for 7 days postconstriction even though a twofold decrease from the maximal response of 344 +/- 129 pg/ml on day 3 to 168 +/- 48 pg/ml on day 7 was observed during this same time interval. Plasma ANF continued to decrease toward prehypertensive levels throughout the remainder of the established phase of the hypertension lasting an additional 21 days of observation. The mechanisms for this observed pattern of plasma ANF are unclear but may involve changes in left atrial distention and stretch as a stimulus for hormone secretion with progression of the hypertension.

Changes of Plasma and Cerebrospinal Fluid Noradrenaline during Frusemide Administration and Acute Renal Artery Constriction in Dogs

1. The effects of circulating angiotensin II on cerebrospinal fluid and plasma noradrenaline during frusemide administration and acute renal artery constriction were studied in dogs. 2. The administration of frusemide produced significant increases in cerebrospinal fluid and plasma noradrenaline. Intravertebral artery infusion of [Sar1, Ala8]angiotensin II (saralasin) significantly suppressed the frusemide-induced increases in cerebrospinal and plasma noradrenaline and resulted in a fall in arterial blood pressure. 3. Acute renal artery constriction produced the marked elevation of plasma noradrenaline and arterial blood pressure, although no significant increase was found in cerebrospinal fluid noradrenaline. Though intravertebral artery infusion of saralasin did not affect cerebrospinal fluid and plasma noradrenaline, intravenous infusion of saralasin reduced the increases in arterial blood pressure and plasma noradrenaline induced by acute renal artery constriction. 4. Plasma volume was significantly reduced by frusemide administration, but unchanged by acute renal artery constriction. 5. Therefore it is suggested that circulating angiotensin II may contribute to the regulation of blood pressure at least partially by acting on the central nervous system in the sodium- and volume-depleted states. However, the renin-angiotensin system appears to play a rather direct role in the mechanism of hypertension induced by renal artery constriction, not through the action of angiotensin II on the central sympathetic nervous system.