Forebrain mechanisms in neurogenic hypertension

In recent years a considerable amount of experimental evidence has suggested that forebrain structures are involved in the pathogenesis of high arterial pressure (AP). However, little is known about the location and function of these supramedullary structures in the hypertensive process. This report reviews a series of studies done to identify the location and to determine the contribution of some forebrain structures to both the development and maintenance of the elevated AP following selective aortic baroreceptor deafferentation (ABD). In the first series of studies, it was demonstrated that the elevated AP resulting from ABD was associated with increased metabolic activity in several forebrain structures: the paraventricular nucleus of the hypothalamus (PVH), supraoptic nucleus, nucleus circularis, median preoptic nucleus, subfornical organ (SFO), and central nucleus of the amygdala. In the second series, bilateral electrolytic lesions of the PVH were shown to prevent the development of and (or) reverse the elevated AP after ABD. Similarly, bilateral microinjections of the neurotoxin kainic acid into the PVH were shown to reverse the increased AP after ABD. In the final series, electrolytic lesions of the SFO were shown to attenuate the rise in AP after ABD and (or) to reduce the elevated AP to a level that remained above control values. Taken together, these data suggest that the PVH and SFO are components of a neuronal circuit involved in the hypertensive process following ABD, and that the SFO likely exerts its effect through the PVH.     

Humoral and neurogenic factors in two-kidney renovascular hypertension

A "bolus" dose (110 microgram) of the angiotesin II (A II)-blocker 1-Sar-8-Ala-A II (Saralasin, S) followed by its slow rate infusion (5 microgram/min/rat) for thirty min, was injected before and after the complete ganglionic blockade by pentolinium (P) in unanaesthetized unilaterally clipped renal hypertensive rats (the opposite kidney remained untouched). Pentolinium was also injected like a "bolus" dose (3 mg) followed by slow infusion (0.1 mg/min/rat) for thirty min. The observations were made until the fifth week after clipping the left renal artery. A consistent maximal hypotensive response was observed after the "bolus test" with both drugs. When S was the first drug injected, an inverse correlation was found between the percent decrease in arterial pressure (BP) by S and the percent decrease in BP by P (r = --0.83, P < 0.01, n = 8). Thus whenever a greater hypotensive effect was obtained by S, a smaller neural pressor component remained to be blocked by P. On the other hand, when P was the first drug injected a lesser A II pressor component remained to be blocked by S in the hypertensive rats. The results suggest that a considerable A II pressor effect in two-kidney renovascular hypertension is mediated via neurogenic mechanisms from the first week. A direct pressor vasoconstriction was found to be significant in cases with very high plasma-renin activity.     

Elevated plasma dopamine beta hydroxylase activity in rats with neurogenic hypertension.

Increased plasma dopamine beta hydroxylase, DBH, activity has been cited as evidence of increased sympathetic function in essential hypertension. Here-to-fore, experimental hypertension in animals has been associated with normal plasma DBH activity. This study shows that rats with neurogenic hypertension, induced by sinoaortic denervation, SAD, have elevated DBH activity; the mean increase in plasma DBH measured 3 days to 11 weeks after operation was 74% higher in the SAD group than in the sham-operated, control group. DBH activity showed a positive correlation with arterial pressure. Mesentery DBH activity was inversely related to plasma enzyme activity in SAD rats, indicating sympathetic nerve terminals in mesentery are a source of plasma DBH. We conclude that plasma DBH activity is an index of increased sympathetic function since it is consistently elevated in rats with neurogenic hypertension resulting from sustained central activation of the sympathetic nervous system.     

Unloading arterial baroreceptors causes neurogenic hypertension

We developed a new model to examine the role of arterial baroreceptors in the long-term control of mean arterial pressure (MAP) in dogs. Baroreceptors in the aortic arch and one carotid sinus were denervated, and catheters were implanted in the descending aorta and common carotid arteries. MAP and carotid sinus pressure (CSP) averaged 104 +/- 2 and 102 +/- 2 mmHg (means +/- 1 SE), respectively, during a 5-day control period. Baroreceptor unloading was induced by ligation of the common carotid artery proximal to the innervated sinus (n = 6 dogs). MAP and CSP averaged 127 +/- 7 and 100 +/- 3 mmHg, respectively, during the 7-day period of baroreceptor unloading. MAP was significantly elevated (P < 0.01) compared to control, but CSP was unchanged. Heart rate and plasma renin activity increased significantly in response to baroreceptor unloading. Removal of the ligature to restore normal flow through the carotid resulted in normalization of all variables. Ligation of the carotid below a denervated sinus (n = 4) caused a significant decrease in CSP but no systemic hypertension. These results indicate that chronic unloading of carotid baroreceptors can produce neurogenic hypertension and provide strong evidence that arterial baroreceptors are involved in the long-term control of blood pressure.     

Prostaglandins,the kidney,and hypertension.

Prostaglandins are part of the family of oxygenated metabolites of arachidonic acid known collectively as eicosanoids. While they are formed, act, and are inactivated locally and rarely circulate in plasma, they can affect blood flow in some tissues and so might contribute to the control of peripheral vascular resistance. Few studies have shown any derangement of total body prostaglandin synthesis or metabolism in hypertension, but increased renal synthesis of one prostanoid, thromboxane A2, has been noted in spontaneously hypertensive rats and some hypertensive humans. This potent vasoconstrictor may account for the increased renal vascular resistance and suppressed plasma renin activity seen in many patients with hypertension. Increased renal vascular resistance could increase the blood pressure directly as a component of total peripheral resistance or indirectly by increasing glomerular filtration fraction and tubular sodium reabsorption. Specific thromboxane synthesis inhibitors not only decrease renal thromboxane production but also increase renal vasodilator prostaglandin synthesis when prostaglandin synthesis is stimulated. This redirection of renal prostaglandin synthesis toward prostacyclin might be of benefit in correcting a fundamental renal defect in patients with hypertension.     

Causes of experimental pulmonary hypertension in rats.

Experimental pulmonary hypertension was induced in young male rats by means of tracheoconstriction and repeated injections of aqueous bean (Phaseolus vulg.) extract into the trachea. After 120 days, the blood pressure of the experimental and control animals was measured in the pulmonary artery with a shaped polyethylene catheter, without opening the chest. In all the experimental animals the blood pressure in the pulmonary artery was higher than in the controls. The mean pressure in the pulmonary artery of the experimental rats was 25 +/- 1 torr and in the controls 16 +/- 0.4 torr. The right ventricle of the experimental animals was larger than in the controls. No difference was found between the systemic blood pressure values, measured in the femoral artery, in the experimental animals and the controls. The experimental animals had a faster heart rate. Cardiac output, measured by the dye dilution method, was the same in the control and experimental animals and there was likewise no difference in the PO2 PCO2 and pH values in the arterial blood. The inhalation of oxygen instead of air did not affect the blood pressure in the pulmonary artery. The pulmonary blood vessels were evaluated quantitatively in histological sections of the experimental and control animal's lungs. There was no different between the thickness of the media of the distal pulmonary vessels, expressed as a percentage of the outer diameter of the vessel, in the experimental animals and the controls. A media thicker than 7% was found in 15% of the evaluated vessels from experimental animals and in 8% of those from the controls. No correlation between the mean thickness of the media and the mean blood pressure in the pulmonary artery was found in any of the animals.